| 1. |
- Hagberg, Johan, 1973, et al.
(författare)
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Konsumtionsrapporten 2023
- 2023
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Rapport (populärvet., debatt m.m.)abstract
- I Konsumtionsrapporten 2023 sammanfattas och analyseras konsumtionen i Sverige under 2022. I den första delen, ”Hushållens konsumtion” ges en översikt över den privata konsumtionen i Sverige och hur den förändrats. Här beskrivs även skillnader mellan olika hushållstyper och konsumentgrupper, hållbarhetsaspekter på konsumtionen samt hushållens framtidsförväntningar på den egna ekonomin. I andra delen, ”Detaljhandeln” beskrivs försäljning och utveckling inom detaljhandeln under 2022 med fokus på olika delbranscher, kanaler och platser, inom e-handeln respektive den butiksbaserade detaljhandeln. Den andra delen avslutas med handelns framtidsförväntningar. Årets Konsumtionsrapport innehåller två fördjupningsdelar som var en och analyserar aktuella teman inom konsumtion. I den första av fördjupningsdelarna analyserar Emma Björner digitalisering inom turism, besöksnäring och upplevelseekonomi. I den andra fördjupningsdelen analyserar och diskuterar Benjamin Hartmann olika exempel på nostalgisk konsumtion.
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| 2. |
- Petersson McIntyre, Magdalena, 1968, et al.
(författare)
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Hur konsumtionen digitaliseras : Texter från forskningsprojektet Digcon - Digitaliseringen av konsumtionskulturen
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Digital teknik håller radikalt på att förändra vår konsumtionskultur. Appar, QR-koder och ständigt mer avancerade mobiltelefoner, samt de digitala spår användningen av dem lämnar efter sig skapar nya konsumtionsbeteenden, nya metoder för marknadsföring och försäljning av produkter, men också nya metoder för forskare att studera konsumtionsmönster. De omformar även vilka vi är som konsumenter. Att forska om den här omvandlingen innebär att undersöka tekniken i sig, de som tillverkar den, de som marknadsför den liksom de som använder den. I forskningsprojektet Digcon – Digitaliseringen av konsumtionskulturen, har forskare från Sverige och Frankrike undersökt olika aspekter av digitalisering och konsumtion. Vilka betydelser har digitala verktyg och apparater i människors vardagsliv och hur förändrar de konsumtionsmönster? Hur påverkar digitaliseringen vad det innebär att vara konsument och hur en konsument uppfattas vara. Hur omformas förståelser av kön, till exempel genom uppkomsten av modebloggar och modeappar? Vilka möjligheter till etisk konsumtion skapas genom digital teknik och vilken etik är det som skapas? I den här rapporten har vi samlat populärvetenskapliga texter från forskningsprojektet. Digcon bedrivs vid Centrum för konsumtionsvetenskap och Centre for retailing, Handelshögskolan vid Göteborgs universitet, Handelshögskolan i Stockholm och Université Tolouse II, Frankrike.
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| 3. |
- Berggren, Olof, et al.
(författare)
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B lymphocytes enhance the interferon-α production by plasmacytoid dendritic cells
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:10, s. 3409-3419
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Type I interferon (IFN) system and B cells are activated in many autoimmune diseases, e.g. systemic lupus erythematosus (SLE). IFNα produced by plasmacytoid dendritic cells (pDC) stimulate several B cell functions, including autoantibody production. However, not much is known how B cells influence the pDC function. We therefore investigated the regulatory effect of B cells on IFNα production by pDC.METHODS:PDC and B cells from healthy blood donor PBMC were stimulated with RNA-containing immune complexes (RNA-IC) consisting of U1 snRNP and IgG from SLE patients, herpes simplex virus (HSV) or oligonucleotide ODN2216, alone or in co-cultures. IFNα, several other cytokines and pDC or B cell-associated surface molecules were analyzed by immunoassays or flow cytometry.RESULTS:B cells enhanced the IFNα production by pDC up to 47-fold, and the effect was most pronounced for pDC stimulated with RNA-IC. Anti-CD31 antibody reduced the RNA-IC-induced IFNα production by 80%, but not when ODN2216 was used as IFN-inducer. Supernatants from ODN2216-stimulated B cells promoted IFNα production by pDC, while supernatants from RNA-IC-stimulated B cells did not.CONCLUSION: Our results reveal a novel B cell function, enhancing the type I IFN production by pDC. Since B cells are activated by type I IFN, this pDC-B cell cross-talk might be of fundamental importance in the etiopathogenesis of SLE, and contribute to a chronic immune activation in SLE and other systemic rheumatic diseases.
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| 4. |
- Berggren, Olof, et al.
(författare)
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Plasmacytoid dendritic cells and RNA-containing immune complexes drive expansion of peripheral B cell subsets with an SLE-like phenotype
- 2017
-
Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:8
-
Tidskriftsartikel (refereegranskat)abstract
- Background Hyperactive B cells and a continuous interferon (IFN)-alpha production by plasmacytoid dendritic cells (pDCs) play a key role in systemic lupus erythematosus (SLE). We asked whether the interaction between B cells and pDCs stimulated with RNA-containing immune complexes affects peripheral B cell subsets. Methods B cells and pDCs were isolated from blood of healthy individuals and stimulated with immune complexes consisting of SLE-IgG and U1snRNP (RNA-IC). Expression of cell surface molecules as well as IL-6 and IL-10 production were determined by flow cytometry and immunoassays. Gene expression profiles were determined by a NanoString nCounter expression array. Results We found a remarkable increase of double negative CD27-IgD-B cells, from 7% within fresh CD19+B cells to 37% in the RNA-IC-stimulated co-cultures of B cells and pDCs, comparable to the frequency of double negative B cells in SLE patients. Gene expression analysis of the double negative CD27-IgD -and the CD27 + IgD-memory B cells revealed that twenty-one genes were differentially expressed between the two B cell subsets (>= 2-fold, p< 0.001). The, IL21R, IL4R, CCL4, CCL3, CD83 and the IKAROS Family Zinc Finger 2 (IKZ2) showed higher expression in the double negative CD27-IgD-B cells. Conclusion The interactions between B cells and pDCs together with RNA-containing IC led to an expansion of B cells with similar phenotype as seen in SLE, suggesting that the pDC-B cell crosstalk contributes to the autoimmune feed-forward loop in SLE.
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| 5. |
- Bjurlid, Filip, 1978-, et al.
(författare)
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Occurrence of brominated dioxins in a study using various firefighting methods
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 599-600, s. 1213-1221
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Tidskriftsartikel (refereegranskat)abstract
- The use of different firefighting methods influences how fast a fire is extinguished and how fast the temperature drops in the area affected by the fire. These differences may also influence the formation of harmful pollutants during firefighting of an accidental fire. The aim was to study occurrence of brominated dibenzo-p-dioxins and furans (PBDD/Fs) in gas and soot during five fire scenarios resembling a small apartment fire and where different firefighting methods were used. Samples of gas and soot were taken both during the buildup of the fire and during the subsequent extinguishing of the fire while using different firefighting methods (nozzle, compressed air foam system, cutting extinguisher) and an extinguishing additive. New containers equipped with identical sets of combustible material were used for the five tests. The use of different firefighting methods and extinguishing additive induced variations in concentration and congener profiles of detected PBDD/Fs. The concentration range of Sigma PBDD/Fs in gas was 4020-18,700 pg/m(3), and in soot 76-4092 pg/m(2). PBDFs were the predominant congeners and 1,2,3,4,6,7,8-HpBDF was the most abundant congener. Chlorinated dibenzo-p-dioxins and furans (PCDD/Fs) were also monitored. The PBDD/Fs contributed with in average 97% to the total (PCDD/Fs plus PBDD/Fs) toxic equivalents, in soot and gas. During extinguishing, the shorter time the temperature was around 300 degrees C, the lower occurrence of PBDD/Fs. In the study the firefighting methods showed a difference in how effectively they induced a temperature decrease below 300 degrees C in the fire zone during quenching, where cutting extinguishing using additive and the compressed air foam system showed the fastest drop in temperature.
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| 6. |
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| 7. |
- Bremell, Daniel, 1978, et al.
(författare)
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Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
- 2013
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited. Methods We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease. Results In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34–11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL. Conclusions We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
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| 8. |
- Cochoy, Franck, 1964, et al.
(författare)
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Digitalizing consumption: Introduction
- 2017
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Ingår i: Cochoy, Franck, Hagberg, Johan, Petersson McIntyre, Magdalena & Sörum, Niklas. (2017). Digitalizing Consumption: How devices shape consumer culture. - : Routledge. - 9781138124899 ; , s. 1-19
-
Bokkapitel (refereegranskat)
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| 9. |
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Digitalizing Consumption: How Devices Shape Consumer Culture
- 2017
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Contemporary consumer society is increasingly saturated by digital technology, and the devices that deliver this are increasingly transforming consumption patterns. Social media, smartphones, mobile apps and digital retailing merge with traditional consumption spheres, supported by digital devices which further encourage consumers to communicate and influence other consumers to consume. Through a wide range of empirical studies which analyse the impact of digital devices, this volume explores the digitization of consumption and shows how consumer culture and consumption practices are fundamentally intertwined and mediated by digital devices. Exploring the development of new consumer cultures, leading international scholars from sociology, marketing and ethnology examine the effects on practices of consumption and marketing, through topics including big data, digital traces, streaming services, wearables, and social media’s impact on ethical consumption. Digitalizing Consumption makes an important contribution to practice-based approaches to consumption, particularly the use of market devices in consumers’ everyday consumer life, and will be of interest to scholars of marketing, cultural studies, consumer research, organization and management.
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| 10. |
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| 11. |
- Elmqvist, Niklas, 1977, et al.
(författare)
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3DVN: A Mixed Reality Platform for Mobile Navigation Assistance
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We present 3DVN, a Mixed Reality platform for navigation assistance in indoor environments. Built on top of a PC-based wearable computer running the Windows operating system, the platform provides a multimodal user interface for navigating in existing physical buildings, including wireless networking, data glove gestural input, voice communication, head-mounted display, and a 3DOF head tracker. Local positioning is performed using a software-only positioning engine making use of WLAN features for accurately pinpointing the mobile device in three dimensions. The 3DVN system has been implemented as a proof-of-concept of a navigation guidance support device for visitors, and has been field-tested with human subjects in the student center of our university. Informal evaluation of subject ratings indicate a strong interest for the new system, both for guests as well as people familiar with the campus and the building.
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| 12. |
- Elmqvist, Niklas, 1977, et al.
(författare)
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3DVN: A Mixed Reality Platform for Mobile Navigation Assistance
- 2007
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Ingår i: ACM CHI2007 Workshop on Mobile Spatial Interaction. ; , s. 1-4
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Konferensbidrag (refereegranskat)abstract
- We present 3DVN, a Mixed Reality platform for navigation assistance in indoor environments. Built on top of a PC-based wearable computer running the Windows operating system, the platform provides a multimodal user interface to navigate existing physical buildings, including wireless networking, data glove gestural input, voice communication, head-mounted display, and a 3DOF head tracker. Local positioning is performed using a software-only WLAN-based engine to accurately pinpoint the mobile device in three dimensions. We use this system as a platform for a simple theoretical framework for classifying interaction for mobile navigation assistance. Informal qualitative evaluation of our system seems to conform to predictions derived from our framework and shows the need for a rich set of interaction components for successful mobile navigation.
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| 13. |
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| 14. |
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| 15. |
- Gericke, Niklas, 1970-, et al.
(författare)
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Conceptual Incoherence as a Result of the use of Multiple Historical Models in School Textbooks
- 2010
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Ingår i: Research in science education. - : Springer Science and Business Media LLC. - 0157-244X .- 1573-1898. ; 40:4, s. 605-623
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores the occurrence of conceptual incoherence in upper secondary school textbooks resulting from the use of multiple historical models. Swedish biology and chemistry textbooks, as well as a selection of books from English speaking countries, were examined. The purpose of the study was to identify which models are used to represent the phenomenon of gene function in textbooks and to investigate how these models relate to historical scientific models and subject matter contexts. Models constructed for specific use in textbooks were identified using concept mapping. The data were further analyzed by content analysis. The study shows that several different historical models are used in parallel in textbooks to describe gene function. Certain historical models were used more often then others and the most recent scientific views were rarely referred to in the textbooks. Hybrid models were used frequently, i.e. most of the models in the textbooks consisted of a number of components of several historical models. Since the various historical models were developed as part of different scientific frameworks, hybrid models exhibit conceptual incoherence, which may be a source of confusion for students. Furthermore, the use of different historical models was linked to particular subject contexts in the textbooks studied. The results from Swedish and international textbooks were similar, indicating the general applicability of our conclusions.
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| 16. |
- Gericke, Niklas, 1970-, et al.
(författare)
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Conceptual Variation in the Depiction of Gene Function in Upper Secondary School Textbooks
- 2010
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Ingår i: Science & Education. - : Springer Science and Business Media LLC. - 0926-7220 .- 1573-1901. ; 19:10, s. 963-994
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores conceptual variation in the depiction of gene function in upper secondary school textbooks. Historically, concepts in genetics have developed in various scientific frameworks, which has led to a level of incommensurability as concepts have changed over time within their respective frameworks. Since students may have difficulties in understanding concepts where there is implicit variation in descriptions of the same phenomena, we have developed a concept mapping instrument and applied it to study the gene function concepts in biology and chemistry textbooks that are widely used in Sweden, and others used in a selection of English speaking countries. The data were then further examined using content analysis. In the present paper we describe the conceptual variation of gene function as it is presented in the textbooks, and analyze the ways in which students’ understanding may be influenced. We conclude that it may be difficult for students to gain a modern, process-oriented understanding of gene function if textbooks are used as foundations for the planning and execution of lessons.
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| 17. |
- Gericke, Niklas, 1970-, et al.
(författare)
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Conceptual Variation or Incoherence? Textbook Discourse on Genes in Six Countries
- 2014
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Ingår i: Science & Education. - Netherlands : Springer Netherlands. - 0926-7220 .- 1573-1901. ; 23:2, s. 381-416
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to investigate in a systematic and comparative way the results of independent studies on the treatment of genes and gene function in high school textbooks from six different countries. We analyze how the conceptual variation within the scientific domain of Genetics regarding gene function models and gene concepts is transformed via the didactic transposition into school science textbooks. The findings indicate that a common textbook discourse on genes and their function exists in textbooks from the different countries. The structure of science as represented by conceptual variation and the use of multiple models was present in all the textbooks. However, the phenomenon of conceptual variation and multiple models is implicit in these textbooks and this brings, as a consequence, the introduction of conceptual incoherence about the gene concept and gene function models within these resources. We conclude that within the textbook discourse on genes found in our study ontological aspects of the academic disciplines of Genetics and Molecular Biology were retained, but without their epistemological underpinnings; these are lost in the didactic transposition. Also within the textbooks explanatory models and concepts that promote a deterministic notion of the gene were found to be most frequent. These results are of interest since students might have problems reconstructing the correct scientific understanding from the transformed school science knowledge as depicted within the high school textbooks. Implications for textbook writing as well as science teaching are discussed in the paper.
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| 18. |
- Gericke, Niklas, et al.
(författare)
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Definition of historical models of gene function and their relation to students' understanding of genetics
- 2007
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Ingår i: Science & Education. - : Springer Science and Business Media LLC. - 0926-7220 .- 1573-1901. ; 16:7-8, s. 849-881
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Tidskriftsartikel (refereegranskat)abstract
- Models are often used when teaching science. In this paper historical models and students’ ideas about genetics are compared. The historical development of the scientific idea of the gene and its function is described and categorized into five historical models of gene function. Differences and similarities between these historical models are made explicit. Internal and external consistency problems between the models are identified and discussed. From the consistency analysis seven epistemological features are identified. The features vary in such ways between the historical models that it is claimed that learning difficulties might be the consequence if these features are not explicitly addressed when teaching genetics. Students’ understanding of genetics, as described in science education literature, is then examined. The comparison shows extensive parallelism between students’ alternative understanding of genetics and the epistemological features, i.e., the claim is strengthened. It is also argued that, when teaching gene function, the outlined historical models could be useful in a combined nature of science and history of science approach. Our findings also raise the question what to teach in relation to preferred learning outcomes in genetics.
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| 19. |
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| 20. |
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| 21. |
- Gericke, Niklas, 1970-
(författare)
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Science versus School-science : Multiple models in genetics - The depiction of gene function in upper secondary textbooks and its influence on students' understanding
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis I describe a study of how the science of genetics is transformed into school science in upper secondary level textbooks and the impact that this transformation has on students’ understanding. The didactic challenge that we face is to decide which science from the academic disciplines we should bring into schools. Using the History and Philosophy of Science as my point of reference, I identified and categorized five multiple historical models of gene function: the Mendelian model, the classical model, the biochemical-classical model, the neoclassical model and the modern model. I then developed a research instrument to be used to analyse how these models are transformed within the educational system via textbooks. Biology and chemistry textbooks from Sweden, as well as a number from English speaking countries, were studied. The models used to describe gene function in the textbooks were investigated, as were the conceptual changes between the actual models and the way they are presented in textbooks. Finally I studied how the transformed science in textbooks is understood by students. I found that all the multiple historical models were used implicitly in the textbooks. The older historical models were presented more frequently, resulting in a simplified and deterministic description of genetics. Throughout the textbooks a specific model was usually described in a particular subject matter context. The models used in the textbooks were usually hybrid models consisting of features from several of the historical models, thus creating incommensurability. The textbooks do not provide any epistemological foundations to facilitate readers’ understanding of the implications of multiple models. Furthermore my results show that, when reading the textbooks, students’ have difficulties in detecting the use of multiple models, incommensurability, and the conceptual changes that occur in a content-specific context such as gene function. Overall, students’ understanding of the use of multiple models, conceptual change, and incommensurability reflects the way in which they are depicted in the textbooks. Students’ domain-specific difficulties in understanding genetics might therefore be due to the way science is transformed into school science. These findings indicate the importance of epistemological aspects in the transformation of science into school science, i.e. science as a way of knowing, not only for students’ understanding of the nature of science, but also for their understanding of the conceptual knowledge. The degree to which school science should mimic the academic discipline, as well as an understanding of what is lost in the transformation of science into school science, are key issues discussed in the thesis.
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| 22. |
- Gericke, Niklas, et al.
(författare)
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Students’ understanding of models in textbooks
- 2010
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Ingår i: Socio-cultural and human values in science and technology education. Proceedings of the XIV symposium of the International Organization for Science and Technology Education (IOSTE). Bled, Slovania, June 13-18, 2010.. - Ljubljana : Institute for Innovation and Development of University of Ljubljana. - 9789619288214 ; , s. 474-482
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Konferensbidrag (refereegranskat)abstract
- In this study 18 to 19 years old upper secondary students' ability to discern the use of multiple models in genetics when reading content specific excerpts in Biology textbooks are investigated. Two excerpts using different models when describing gene function was selected from authentic textbooks and nine students were given the specific task of reading the excerpts. Afterwards the students participated in semi-structured interviews. The main theme of the interview was about how the students experienced the similarities and differences between the texts, and how they understood models and conceptual change in genetics. Students recognized the existence of multiple models in a general way, but had difficulties discerning the different models and the conceptual change that occurs between them in the texts. Students had difficulties in transforming their general knowledge about multiple models into understanding of content specific models of gene function in the textbooks. These findings may have implications for students' understanding of conceptual knowledge since research has established textbooks as one of the most influential aspects in the planning and execution of biology lessons.
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| 23. |
- Gericke, Niklas, 1970-, et al.
(författare)
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Students’ understanding of models in textbooks
- 2010
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Ingår i: XIV IOSTE Symposium, Bled, Slovenia, conference proceedings. - : IRI UL, Institute for innovation and Development of University of Ljubljana. - 9789619288214
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Konferensbidrag (refereegranskat)
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Gericke, Niklas, 1970-, et al.
(författare)
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Upper secondary students’ understanding of the use of multiple models in biology textbooks : The importance of conceptual variation and incommensurability
- 2013
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Ingår i: Research in science education. - : Springer. - 0157-244X .- 1573-1898. ; 43:2, s. 755-780
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Tidskriftsartikel (refereegranskat)abstract
- In this study we investigate students' ability to discern conceptual variation and the use of multiple models in genetics when reading content-specific excerpts from biology textbooks. Using the history and philosophy of science as our reference, we were able to develop a research instrument allowing students themselves to investigate the occurrence of multiple models and conceptual variation in Swedish uppersecondary textbooks. Two excerpts using different models of gene function were selected from authentic textbooks. Students were given the same questionnaire-instrument after reading the two texts, and the results were compared. In this way the students themselves made a classification of the texts which could then be compared with the researchers' classification of the texts. Forty-one upper secondary students aged 18-19 participated in the study. Nine of the students also participated in semi-structured interviews. Students recognized the existence of multiple models in a general way, but had difficulty discerning the different models and the conceptual variation that occurs between them in the texts. Further they did not recognize the occurrence of incommensurability between multiple models. Students had difficulty in transforming their general knowledge of multiple models into an understanding of content specific models of gene function in the textbooks. These findings may have implications for students'understanding of conceptual knowledge because research has established textbooks as one of the most influential aspects in the planning and execution of biology lessons, and teachers commonly assign reading passages to their students without further explanation.
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| 29. |
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| 30. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
- 2016
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 3, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. Methods: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. Findings: Plasma and CSF NFL concentrations were very highly correlated (r=0.89, P<0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4+ T cells. Interpretation: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.
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| 31. |
- Hagberg, Johan, et al.
(författare)
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Digitalization of retailing : Beyond e-commerce
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- ”Digitalization” is one of the greatest transformation of contemporary society. The on-going changes due to digitalization are not least important in the retail sector, which both affects and is affected by the development. The Internet’s entry has resulted in new business opportunities (e.g. Quelch & Klein, 1996), new companies (e.g. Mols, 2000), business models (e.g. Sorescu et al., 2011) and forms of commerce (e.g. Gloor, 2000). So far in retailing, digitalization and the Internet has primarily been discussed in terms of an increased presence of e-commerce. However, the Internet is becoming more and more integrated in all forms of retailing and the impact of digitalization goes far beyond the phenomena of e-commerce. The transformation of previously physical products into digital services, the use of digital devices in various steps of the purchasing process as well as consumer recommendations and communications through social media are all examples of much broader and vigorous impacts. In recent years the increasing use of digital mobile devices with Internet has started to transform consumer practices in general including shopping behaviour. New consumer products with mobile Internet are launched at a rapid pace and variety of mobile products and technologies are becoming interlinked (see e.g. Cochoy, 2012). With these mobile devices Internet is also increasingly becoming an element in physical stores (Bodhani 2012). Information retrieval, testing, ordering, payment and service and be done in different channels, and new retail formats such as pop-up stores (Kim et al 2010), click-and-drive (Colla & Lapule, 2012) and others are developed as we speak. New apps are developed for payments (e.g. iZettle), price comparisons (e.g. Pricerunner) or product information (e.g. Good Guide). This broader development will probably have far-reaching effects for retailers, consumers, employees, and suppliers. There is a great need for knowledge about this transformation and its effects (Grewal & Levy, 2009; Doherty & Ellis-Chadwick, 2010; Hagberg et al, 2012). While research on e-commerce is vast and has been extensive already from the outset (e.g. Alba et al., 1997; Burke, 1997; Reynolds, 2000; Bakos, 2001; Burt & Sparks, 2003), retailing research has so far largely ignored the more all-encompassing transformations of digitalization. While scholars have recognized the relevance of the Internet for physical stores, retail formats, apps and so on, there is a paucity of studies that has systematically analyzed the implications of these developments for retailing. Such analysis is central given the potentially far-reaching effects that digitalization could have in the retail industry. Thus, the need to develop a framework that could be used to problematize the consequences of digitization in a retail context is clear. The purpose of this paper is to analyze how retailing is transformed due to digitalization and to develop research propositions on the consequences of these transformations. This paper analyses the digitalization of retailing starting from the retailer-consumer exchange interface, and more specifically along three various facets of exchange: communication, transaction and distribution (Peterson et al., 1997). Communication concerns the access to and exchange of information. Transactions concern the transfer of ownership including monetary transactions, and the actual purchase. Distribution refers to the physical and tangible exchanges of products. In turn, these three facets of exchange are broken down into subcategories, which are further developed with examples from Swedish retailing in order to provide a more detailed understanding of how digitalization transforms retailing in various areas. Conseque4nces are identified and research proposals are developed based on three different “levels” of retailing; micro, meso, and macro, reaching from individual retail employees to societal changes. Among key consequences it is pointed out that digital literacy and skills in the workplace will be a key challenge while also calling for novel forms of knowledge transfer among employees; that the transformations will put pressure on retailers to modify and develop new business models that take challenges and opportunities of digitalization into account; and that it will affect retailers ability to be cost-effective, sustainable and attractive to consumers. In addition to transforming retailing in several ways, the changes imposed by the digitalization may also have consequences for the role retailing will play in society.
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| 32. |
- Hagberg, Johan, 1973, et al.
(författare)
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Digitalization of retailing: A review and framework
- 2015
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Ingår i: 18th EAERCD Conference Rennes, France 1-3 July 2015. - 9782746684515
-
Konferensbidrag (refereegranskat)abstract
- ‘Digitalization’ is one of the most significant ongoing transformations of contemporary society and encompasses many aspects of business and everyday life. These transformations are especially important for the retail sector as it both affects and is affected by the development. So far, scholarly conversation about retailing’s digitalization has been voluminous but relatively limited to specific aspects of digitalization, e.g., e-commerce. The purpose of this paper is to systematically analyse how retailing has transformed and is being transformed due to digitalization. This is done by reviewing and discussing the literature and developing a framework comprising four elements: exchanges, actors, offerings, and settings. It is argued that digitalization transforms: i) the retailing exchanges in a number of ways and in various facets of exchange: communications, transactions, and distribution; ii) the nature of retail offerings, and leads to blurred distinctions between products and services and what constitutes the actual offering; iii) the retail settings, i.e., where and when retailing takes place; and iv) the actors participating in retailing, i.e. retailers, consumers, and other parties. The article proposes that these elements are mutually reinforcing, which leads to a certain dynamic and far-reaching transformations due to digitalization. It is concluded that digitalization, far from being restricted to e-commerce, is more or less transforming all areas of retailing, which will possibly also have implications for the very definition of retailing.
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| 33. |
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| 34. |
- Hagberg, Johan, 1973, et al.
(författare)
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Konsumtionsrapporten 2022
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Konsumtionsrapporten 2022 sammanfattas och analyseras konsumtionen i Sverige under 2021 och merparten av 2022. I den första delen, ”Hushållens konsumtion” ges en översikt över den privata konsumtionen i Sverige, hur den har förändrats i såväl kortare som längre perspektiv samt hushållens framtidstro avseende sin egen och Sveriges ekonomi. I andra delen, ”Detaljhandeln” beskrivs försäljning och utveckling inom detaljhandeln under 2021 och inledningen av 2022 med fokus på olika delbranscher, kanaler och platser, e-handeln respektive den butiksbaserade detaljhandeln. Den andra delen avslutas med handelns framtidsförväntningar. Den tredje delen ”Framtidsutsikter” tar avstamp i konsumenters och handelns framtidsförväntningar från de två första delarna och fördjupar analysen av framtidsutsikter utifrån publicerade prognoser och uttalanden från ekonomiska bedömare. Årets rapport innehåller tre fördjupningsdelar som var en och analyserar aktuella teman inom konsumtion. Under lång tid har det skett en ökad digitalisering av konsumtionen och inte minst under pandemin har många konsumtionsbeteenden förskjutits mot en allt större användning av internet och olika digitala gränssnitt som till exempel webshopar, social media och strömningstjänster. I takt med detta har det också väckts många frågor som berör säkerhet och personlig integritet online. I den första av fördjupningsdelarna analyserar Jeanette Carlsson Hauff konsumenters upplevda fördelar och risker avseende digital integritet vid användning av olika digitala tjänster. I den andra fördjupningsdelen visar Niklas Sörum på konsumenters olika förhållningssätt till datainsamling och datadriven marknadsföring. Andra konsumtionsbeteenden som aktualiserats under de senaste åren är olika typer av reaktioner på eller förberedelser inför kriser i termer av bunkring, hamstring och prepping. I den tredje delen analyserar och diskuterar Elias Mellander olika exempel på kriskonsumtion och hemberedskap.
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| 35. |
- Hagberg, Johan, 1973, et al.
(författare)
-
Konsumtionsrapporten 2024
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Konsumtionsrapporten 2024 sammanfattas och analyseras konsumtionen i Sverige under 2023. I den första delen, ”Hushållens konsumtion” ges en översikt över den privata konsumtionen i Sverige och hur den förändrats. Här beskrivs även hållbarhetsaspekter på konsumtionen samt hushållens framtidsförväntningar på den egna ekonomin. I andra delen, ”Detaljhandeln” beskrivs försäljning och utveckling inom detaljhandeln under 2023 med fokus på olika delbranscher, kanaler och platser, inom e-handeln respektive den butiksbaserade detaljhandeln. Den andra delen avslutas med handelns framtidsförväntningar. Årets Konsumtionsrapport innehåller två fördjupningsdelar som var en och analyserar aktuella teman inom konsumtion. I den första av fördjupningsdelarna diskuterar Magdalena Petersson McIntyre och Emma Björner lyxkonsumtionens utveckling, status, hållbarhet och moral. I den andra fördjupningsdelen belyser Karin M. Ekström kulturkonsumtion med fokus på konstutställningar.
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| 36. |
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| 37. |
- Hagberg, Johan, 1973, et al.
(författare)
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The digitalization of retailing: an exploratory framework
- 2016
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Ingår i: International Journal of Retail & Distribution Management. - 0959-0552 .- 1758-6690. ; 44:7, s. 694-712
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Tidskriftsartikel (refereegranskat)abstract
- AbstractPurpose – Digitalization denotes an on-going transformation of great importance for the retail sector. The purpose of this paper is to analyse the phenomenon of the digitalization of retailing by developing a conceptual framework that can be used to further delineate current transformations of the retailerconsumer interface.Design/methodology/approach – This paper develops a framework for digitalization in the retail-consumer interface that consists of four elements: exchanges, actors, offerings, and settings. Drawing on the previous literature, it describes and exemplifies how digitalization transforms each of these elements and identifies implications and proposals for future research.Findings – Digitalization transforms the following: retailing exchanges (in a number of ways and in various facets of exchange, including communications, transactions, and distribution); the nature of retail offerings (blurred distinctions between products and services, what constitutes the actual offering and how it is priced); retail settings (i.e. where and when retailing takes place); and the actors who participate in retailing (i.e. retailers and consumers, among other parties).Research limitations/implications – The framework developed can be used to further delineate current transformations of retailing due to digitalization. The current transformation has created challenges for research, as it demands sensitivity to development over time and insists that categories that have been taken for granted are becoming increasingly blurred due to greater hybridity.Originality/value – This paper addresses a significant and on-going transformation in retailing and develops a framework that can both guide future research and aid retail practitioners in analysing retailing’s current transformation due to digitalization.
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| 38. |
- Hagberg, Niklas, et al.
(författare)
-
Anti-NKG2A autoantibodies in a patient with systemic lupus erythematosus
- 2013
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 52:10, s. 1818-1823
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo characterize a novel anti-NKG2A autoantibody detected in a patient with SLE during a severe flare, and in a cross-sectional study investigate the occurrence of such autoantibodies in patients with SLE and primary SS (pSS).MethodsSerum or IgG from patients with SLE, pSS and healthy volunteers were assayed for blocking of anti-NKG2A or HLA-E binding to peripheral blood mononuclear cells or CD94/NKG2A- and CD94/NKG2C-transfected Ba/F3 cells. The anti-NKG2A autoantibodies were evaluated for effect on NK cell degranulation in response to HLA-E-transfected K562 cells. IFN-α was determined by an immunoassay and disease activity by the SLEDAI score.ResultsAnti-NKG2A autoantibodies, which blocked binding of HLA-E tetramers to CD94/NKG2A-transfected cells and impaired NKG2A-mediated inhibition of NK cell activation, were observed in a patient with SLE. The presence of anti-NKG2A autoantibodies was associated with high SLE disease activity (SLEDAI score 14 and 16) and increased serum IFN-α. Of 94 SLE, 60 pSS and 30 healthy donor sera, only the index patient serum contained anti-NKG2A autoantibodies.ConclusionThe presence of autoantibodies targeting NKG2A is a rare event, but when such autoantibodies occur they may promote excessive NK cell function. This can contribute to the pathogenesis by increasing the killing of cells and the release of autoantigens. Our findings highlight the possible importance of NK cells in the SLE disease process.
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| 39. |
- Hagberg, Niklas, 1977-, et al.
(författare)
-
Autoantibodies to the CD94/NKG2A and CD94/NKG2C receptors in patients with systemic lupus erythematosus
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To investigate the occurrence and function of autoantibodies (autoabs) targeting the CD94/NKG2A, CD94/NKG2C or NKG2D receptors in patients with systemic lupus erythematosus (SLE).Method: Murine Ba/F3 cells transfected with CD94/NKG2A, CD94/NKG2C or NKG2D, and untransfected cells were incubated with sera from 203 patients with SLE and 90 healthy individuals. Binding of immunoglobulin (Ig) to the cells was determined by flow cytometry. Autoabs were characterized with regard to isotype, subclass, λ/κ exclusion and interference with HLA-E-binding. IgG were evaluated for effect on NK cell degranulation in response to HLA-E-transfected K562 target cells, as well as their capacity to induce antibody-dependent cellular cytotoxicity (ADCC). The frequency and phenotype of NK cells from these patients were determined by flow cytometry and the exons encoding NKG2A (KLRC1), NKG2C (KLRC2) and CD94 (KLRD1) were sequenced. The titers of anti-CD94/NKG2A and -CD94/NKG2C autoabs were determined in longitudinally sampled sera and correlated to disease activity (SLEDAI score) and severity (SLICC/ACR damage index).Results: Seven patients with autoabs targeting the CD94/NKG2A receptor were identified. Two of these patients’ autoabs also recognized the CD94/NKG2C receptor. IgG from six of the patients interfered with the binding of HLA-E to CD94/NKG2A, whereas IgG from one patient increased this binding. Of the two patients with anti-CD94/NKG2C autoabs, IgG from one patient blocked, and IgG from the other patient stabilized the binding of HLA-E to CD94/NKG2C. Anti-CD94/NKG2A autoabs abrogated the HLA-E-mediated inhibition of NK cell cytotoxicity by CD94/NKG2A+ NK cells, whereas anti-CD94/NKG2C autoabs interfered with the HLA-E-mediated increased cytotoxicity of CD94/NKG2C+ NK cells. Furthermore, these autoabs induced ADCC of CD94/NKG2A- and CD94/NKG2C-expressing target cells. No uncommon non-synonymous sequence variations were found in the genes encoding NKG2A, NKG2C or CD94. The titers of anti-CD94/NKG2A and -CD94/NKG2C autoabs were associated to the SLEDAI score.Conclusions: Autoabs targeting the CD94/NKG2A or the CD94/NKG2C receptor are found in a subset of patients with SLE. These autoabs affects the cytotoxicity of NK cells, mediate ADCC in vitro and their titers are associated to the disease activity and a more severe SLE phenotype. Consequently, anti-CD94/NKG2A and anti-CD94/NKG2C autoabs may contribute to the pathogenesis of SLE and our findings highlight the possible importance of NK cells in the SLE disease process.
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| 40. |
- Hagberg, Niklas, et al.
(författare)
-
Functional Anti-CD94/NKG2A and Anti-CD94/NKG2C Autoantibodies in Patients With Systemic Lupus Erythematosus
- 2015
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Ingår i: ARTHRITIS & RHEUMATOLOGY. - : Wiley. - 2326-5191 .- 2326-5205. ; 67:4, s. 1000-1011
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Recently we serendipitously identified a patient with systemic lupus erythematosus (SLE) who was positive for autoantibodies to CD94/natural killer receptor group 2A (NKG2A). The present study was undertaken to investigate the occurrence and function of autoantibodies targeting lectin-like NK cell receptors in SLE. Methods. Sera from 203 SLE patients and 90 healthy individuals were analyzed, by flow cytometry, for Ig binding to Ba/F3 cells transfected with CD94/NKG2A, CD94/NKG2C, or NKG2D. Autoantibodies identified were characterized with regard to interference with HLA-E binding, effect on NK cell activation in response to HLA-E-transfected K562 cells, and capacity to facilitate antibody-dependent cell-mediated cytotoxicity (ADCC). Levels of autoantibodies were determined in longitudinally sampled sera, and correlations with disease activity (SLE Disease Activity Index 2000) and severity (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were investigated. Results. Anti-CD94/NKG2A autoantibodies were identified in 7 SLE patients. The autoantibodies from 6 patients inhibited binding of HLA-E to CD94/NKG2A, whereas those from the seventh patient augmented this binding. Autoantibodies from 2 patients also reacted with the activating receptor CD94/NKG2C, with inhibition of the binding of HLA-E to CD94/NKG2C observed in 1 case and enhancement of this binding in the other. None of the sera contained anti-NKG2D autoantibodies. The levels of anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies correlated with disease activity and with a more severe SLE phenotype. Mechanistically, anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies both interfered with HLA-E-mediated regulation of NK cell activation and facilitated the elimination of target cells expressing CD94/NKG2A or CD94/NKG2C through ADCC. Conclusion. Anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies occur in a subset of patients with clinically active SLE. Given their capacity to deplete certain NK cell subsets and interfere with particular NK cell function, such autoantibodies may promote the pathogenesis of SLE.
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| 41. |
- Hagberg, Niklas, et al.
(författare)
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IFN-α Production by Plasmacytoid Dendritic Cells Stimulated with RNA-Containing Immune Complexes Is Promoted by NK Cells via MIP-1β and LFA-1
- 2011
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 186:9, s. 5085-5094
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Tidskriftsartikel (refereegranskat)abstract
- Several systemic autoimmune diseases display a prominent IFN signature. This is caused by a continuous IFN-α production by plasmacytoid dendritic cells (pDCs), which are activated by immune complexes (ICs) containing nucleic acid. The IFN-α production by pDCs stimulated with RNA-containing IC (RNA-IC) consisting of anti-RNP autoantibodies and U1 small nuclear ribonucleoprotein particles was recently shown to be inhibited by monocytes, but enhanced by NK cells. The inhibitory effect of monocytes was mediated by TNF-α, PGE2, and reactive oxygen species, but the mechanisms for the NK cell-mediated increase in IFN-α production remained unclear. In this study, we investigated the mechanisms whereby NK cells increase the RNA-IC–induced IFN-α production by pDCs. Furthermore, NK cells from patients with systemic lupus erythematosus (SLE) were evaluated for their capacity to promote IFN-α production. We found that CD56dim NK cells could increase IFN-α production >1000-fold after RNA-IC activation, whereas CD56bright NK cells required costimulation by IL-12 and IL-18 to promote IFN-α production. NK cells produced MIP-1α, MIP-1β, RANTES, IFN-γ, and TNF-α via RNA-IC–mediated FcγRIIIA activation. The IFN-α production in pDCs was promoted by NK cells via MIP-1β secretion and LFA-mediated cell–cell contact. Moreover, NK cells from SLE patients displayed a reduced capacity to promote the RNA-IC–induced IFN-α production, which could be restored by exogenous IL-12 and IL-18. Thus, different molecular mechanisms can mediate the NK cell-dependent increase in IFN-α production by RNA-IC–stimulated pDCs, and our study suggests that the possibility to therapeutically target the NK–pDC axis in IFN-α–driven autoimmune diseases such as SLE should be investigated.
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| 42. |
- Hagberg, Niklas, 1977-, et al.
(författare)
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Immunogenetics in systemic lupus erythematosus : Transitioning from genetic associations to cellular effects
- 2020
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 92:4, s. e12894-
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Systemic lupus erythematosus (SLE) is a heterogeneous rheumatic autoimmune disease. Genetic studies have identified up to 100 SLE risk loci. Many of these encode proteins of importance in the immune system, but the cellular and molecular mechanisms underlying these associations are still elusive. In this review, we will highlight some of the SLE risk loci where mechanistic insights have been achieved recently by linking genetic risk polymorphisms to cellular or molecular phenotypes important for the disease process.
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| 43. |
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| 44. |
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| 45. |
- Hagberg, Niklas, et al.
(författare)
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Systemic lupus erythematosus : a disease with a dysregulated type I interferon system
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 82:3, s. 199-207
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Forskningsöversikt (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the loss of tolerance to nuclear antigens, immune complex formation and inflammation in multiple organs. The disease is very heterogeneous and most clinicians consider SLE as a group of diseases with similar features where the pathogenesis is driven by a combination of genetic and environmental factors. One of the most prominent features, shared by the majority of SLE patients, is a continuous activation of the type I interferon (IFN) system, which manifests as increased serum levels of IFNα and/or an increased expression of type I IFN induced genes, a so called type I IFN-signature. The mechanisms behind this IFN-signature have partly been clarified during recent years, although the exact function of the IFN regulated genes in the disease process is unclear. In this review we will describe the type I IFN system and its regulation and summarize the numerous findings implicating an important ethiopathogenic role of a dysregulated type I IFN system in SLE. Furthermore, strategies to therapeutically target the type I IFN system that are currently evaluated preclinically and in clinical trials will be mentioned.
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| 46. |
- Hagberg, Niklas, et al.
(författare)
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Systemic Lupus Erythematosus Immune Complexes Increase the Expression of SLAM Family Members CD319 (CRACC) and CD229 (LY-9) on Plasmacytoid Dendritic Cells and CD319 on CD56(dim) NK Cells
- 2013
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 191:6, s. 2989-2998
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with systemic lupus erythematosus (SLE) display an activated type I IFN system due to unceasing IFN-a release from plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). NK cells strongly promote the IFN-a production by pDCs; therefore, we investigated surface molecules that could be involved in the pDC-NK cell cross-talk. In human PBMCs stimulated with RNA-containing ICs (RNA-ICs), the expression of the signaling lymphocyte activation molecule (SLAM) family receptors CD319 and CD229 on pDCs and CD319 on CD56(dim) NK cells was selectively increased. Upregulation of CD319 and CD229 on RNA-IC-stimulated pDCs was induced by NK cells or cytokines (e. g., GM-CSF, IL-3). IFN-alpha-producing pDCs displayed a higher expression of SLAM molecules compared with IFN-a 2 pDCs. With regard to signaling downstream of SLAM receptors, pDCs expressed SHIP-1, SHP-1, SHP-2, and CSK but lacked SLAM-associated protein (SAP) and Ewing's sarcoma-activated transcript 2 (EAT2), indicating that these receptors may act as inhibitory receptors on pDCs. Furthermore, pDCs from patients with SLE had decreased expression of CD319 on pDCs and CD229 on CD56 dim NK cells, but RNA-IC stimulation increased CD319 and CD229 expression. In conclusion, this study reveals that the expression of the SLAM receptors CD319 and CD229 is regulated on pDCs and NK cells by lupus ICs and that the expression of these receptors is specifically altered in SLE. These results, together with the observed genetic association between the SLAM locus and SLE, suggest a role for CD319 and CD229 in the SLE disease process.
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| 47. |
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| 48. |
- Hagberg, Niklas, et al.
(författare)
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The Interferon System in Lupus Erythematosus
- 2016
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Ingår i: Systemic Lupus Erythematosus. - : Academic Press. - 9780128020098 - 9780128019177 ; , s. 153-158
-
Bokkapitel (refereegranskat)abstract
- The interferons (IFNs) are a large group of proteins classified into three types (I-III) that induce viral resistance in cells and also act as immune adjuvants and stimulate the adaptive immune system. Increased levels of mainly type I IFN are seen in patients with systemic lupus erythematosus (SLE), which is due to the presence of self-derived inducers of type I IFN production acting on plasmacytoid dendritic cells. Such inducers consist of autoantigens containing nucleic acid that stimulate endosomal Toll-like receptors, which trigger the ongoing IFN synthesis that leads to an increased transcription of type I IFN-regulated genes in target cells (an interferon signature). The type I IFN production contributes to the autoimmune process and several therapies aiming to inhibit the production, or action, of type I IFN have been developed. Preliminary results indicate that this therapeutic strategy may be successful in a subset of patients with SLE.
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| 49. |
- Hagberg, Niklas, 1977-
(författare)
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The Role of Plasmacytoid Dendritic Cells and Natural Killer Cells in Systemic Lupus Erythematosus
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production, which can eventually lead to immune complex (IC)-mediated organ damage. Due to the stimulation of plasmacytoid dendritic cells (pDC) by nucleic acid-containing ICs (DNA- or RNA-IC), patients with SLE have an ongoing interferon (IFN)-α production. IFN-α induces a general activation of the immune system that may initiate or propagate an autoimmune process if not properly regulated. Previous studies have shown that natural killer (NK) cells potently enhance the IFN-α production by pDCs.In study I, the mechanisms behind the NK cell-mediated increased IFN-α production by RNA-IC-stimulated pDCs were investigated. ICs triggered CD56dim NK cells via FcγRIIIA to the secretion of cytokines (e.g. MIP-1β) that promoted IFN-α production. Additionally, an LFA-1-dependent cell-cell interaction between pDCs and NK cells strongly contributed to the increased production of IFN-α. In study II, the RNA-IC-induced regulation of surface molecules on pDCs and NK cells was investigated. The expression of CD319 and CD229, which are two SLAM family receptors genetically associated with SLE, was induced on pDCs and NK cells by RNA-IC. IFN-α-producing pDCs displayed an increased expression of CD319 and CD229, whereas pDCs from patients with SLE had a decreased expression of CD319. In study III, we serendipitously identified an SLE patient harboring autoantibodies to the NK cell receptor CD94/NKG2A. In study IV, sera from 203 patients with SLE were analyzed for autoantibodies to the CD94/NKG2A, CD94/NKG2C and NKG2D receptors. Seven patients harbored anti-CD94/NKG2A autoantibodies, and two of these patient’s autoantibodies also reacted with CD94/NKG2C. Anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies both interfered with the HLA-E-mediated regulation of NK cell cytotoxicity, and facilitated the elimination of target cells expressing these receptors. Furthermore, these autoantibodies were found in a group of severely diseased SLE patients and their titers closely followed disease activity.In conclusion, this thesis provides insights to molecular mechanisms whereby NK cells regulate the IFN-α production, it further links the SLAM receptors to SLE, and it describes novel autoantibodies to receptors regulating NK cell cytotoxicity. Together these findings strengthen the assumption that NK cells are involved in the pathogenesis of SLE.
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| 50. |
- Hagberg, Niklas, 1977-, et al.
(författare)
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The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:7, s. 1070-1077
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs.Results In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively.Conclusions T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.
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