| 1. |
- Mazzurana, Luca, et al.
(författare)
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Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
- 2021
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Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:5, s. 554-568
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Tidskriftsartikel (refereegranskat)abstract
- The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
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| 2. |
- Appelgren, Daniel, et al.
(författare)
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Active NET formation in Libman–Sacks endocarditis without antiphospholipid antibodies : A dramatic onset of systemic lupus erythematosus
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:6, s. 310-318
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Tidskriftsartikel (refereegranskat)abstract
- Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman–Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman–Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sex-matched blood donors (p =.0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r = 0.65, p =.16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman–Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE.
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| 3. |
- Hagström, Charlotte, et al.
(författare)
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På cykel mot friheten : cykelkurser för vuxna
- 2019
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Ingår i: Kultur X : 10-talet i kulturvetenskaplig belysning - 10-talet i kulturvetenskaplig belysning. - 2001-7529. - 9789198545920 - 9789198545937 ; 24, s. 145-159
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Bokkapitel (refereegranskat)abstract
- I Sverige lär sig de flesta barn cykla innan de börjar skolan och det tas mer eller mindre för givet att alla vuxna kan cykla. Men långt ifrån alla kan. År 2016 startade Cykelfrämjandet projektet ”Frihet på cykel” då intresset av att lära sig cykla och behovet av cykelkurser ökade allt mer. I artikeln, som bygger på ett fältarbete vid cykelkurser för vuxna i Malmö och Stockholm och intervjuer med deltagare och instruktörer, diskuteras cyklingens betydelse både ur ett individuellt och samhälleligt perspektiv. Varför är det viktigt att kunna cykla? Varför har deltagarna, som huvudsakligen är kvinnor födda utanför Sverige, inte lärt sig tidigare och varför vill de lära sig nu? Varför startas cykelkurser under 2010-talet? Finns det paralleller, och i så fall vilka och varför, till 1910-talet och den cykelkultur som då växte sig allt starkare?
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| 4. |
- Höög, Charlotte
(författare)
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Capsule endoscopy in the diagnosis of small bowel disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Capsule endoscopy (CE) is a method for examining the small bowel by means of an ingested encapsulated video camera, propelled by peristalsis, to continuously take images during its passage through the gastrointestinal tract. The method has been in clinical use in Sweden since 2002 and is considered user-friendly and well tolerable by patients. CE is used to diagnose obscure small-bowel bleeding, Crohn´s disease (CD) and suspected small-bowel tumors. It is known for having a high sensitivity but a lower specificity. In study I CE was performed in 18 patients with chronic intestinal dysmotility (CID), in which a high frequency of mucosal breaks (89%) was observed. There were signs of motility disturbances but the small-bowel transit time did not differ significantly between the two types of CID or to a control group. This was the first study to use CE in CID patients. CE was shown to be feasible for the examination of small bowel mucosa in patients with CID. When CE is used to find a bleeding source in the small bowel, the most common finding are vascular malformations; angioectasias. These can also be found in non-bleeding patients but what triggers bleeding in some patients is not fully understood. In study II a group of 25 patients with bleeding from gastrointestinal angioectasias were tested for bleeding disorders with special focus on acquired von Willebrand syndrome (AVWS), a condition previously identified as a possible explanation for bleeding. Compared to a control group, no significant differences between groups were found in coagulation parameters, bleeding time or von Willebrand multimer levels. These results did not support the need for routine bleeding tests in cases of bleeding from angioectasias and do not demonstrate an overall increased risk of AVWS among these patients. Inflammatory lesions in the small bowel showed by CE may be due to CD but also to other conditions. Since biopsies from the small bowel might be difficult to obtain the relevance of the lesions may remain unclear. In study III 30 patients with small bowel lesions were tested for inflammatory markers in blood (CRP) and faeces (calprotectin). Harvey-Bradshaw Index (HBI) was used to grade patient symptoms. The patients were followed up after nine months with a second capsule endoscopy, CRP, calprotectin and HBI. A significant correlation was found between endoscopic inflammation and calprotectin that persisted over time. A correlation between endoscopic inflammation and CRP was found at inclusion but did not persist at follow up. Symptoms did not correlate with endoscopic findings of inflammation at any time. Study IV aimed to evaluate complications of capsule endoscopy, specifically incomplete examinations and capsule retention and to determine the risk factors for these. In this consecutive study 2300 CE examinations - performed at four different hospitals in Stockholm, Sweden from 2003 to 2009 - were included. The frequency of incomplete examinations was 20%. Older age, male gender and suspected or known CD were risk factors for an incomplete examination. Capsule retention occurred in 1.3%. Risk factors for capsule retention were known CD and a suspected tumor. CE was concluded to be an overall safe procedure, although obstructive symptoms and serious complications due to capsule retention can be found in large patient series.
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| 5. |
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| 6. |
- Mazzurana, Luca, et al.
(författare)
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Suppression of Aiolos and Ikaros expression by lenalidomide reduces human ILC3−ILC1/NK cell transdifferentiation
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 202:1
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Tidskriftsartikel (refereegranskat)abstract
- The Ikaros family of transcription factors (TFs) are important regulators of lymphocyte function. However, their roles in human innate lymphoid cell (ILC) function remain unclear. Here, we found that Ikaros (IKZF1) is expressed by all ILC subsets, including NK cells, in blood, tonsil, and gut, while Helios (IKZF2) is preferentially expressed by ILC3 in tonsil and gut. Aiolos (IKZF3) followed the expression pattern of T-bet and Eomes, being predominantly expressed by ILC1 and NK cells. Differentiation of IFN-γ-producing ILC1 and NK cells from ILC3 by IL-1β plus IL-12-stimulation was associated with upregulation of T-bet and Aiolos. Selective degradation of Aiolos and Ikaros by lenalidomide suppressed ILC1 and NK cell differentiation and expression of ILC1 and NK cell-related transcripts (LEF1, PRF1, GRZB, CD244, NCR3, and IRF8). In line with reduced ILC1/NK cell differentiation, we observed an increase in the expression of the ILC3-related TF Helios, as well as ILC3 transcripts (TNFSF13B, IL22, NRP1, and RORC) and in the frequency of IL-22 producing ILC3 in cultures with IL-1β and IL-23. These data suggest that suppression of Aiolos and Ikaros expression inhibits ILC1 and NK cell differentiation while ILC3 function is maintained. Hence, our results open up for new possibilities in targeting Ikaros family TFs for modulation of type 1/3 immunity in inflammation and cancer.
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| 7. |
- Nyström, Monica E., et al.
(författare)
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Healthcare system intervention for prevention of birth injuries : process evaluation of self-assessment, peer review, feedback and agreement for change
- 2012
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patient safety is fundamental in high quality healthcare systems but despite an excellent record of perinatal care in Sweden some children still suffer from substandard care and unnecessary birth injuries. Sustainable patient safety improvements assume changes in key actors' mental models, norms and culture as well as in the tools, design and organisation of work. Interventions positively affecting team mental models on safety issues are a first step to enhancing change. Our purpose was to study a national intervention programme for the prevention of birth injuries with the aim to elucidate how the main interventions of self-assessment, peer review, feedback and written agreement for change affected the teams and their mental model of patient safety, and thereby their readiness for change. Knowledge of relevant considerations before implementing this type of patient safety intervention series could thereby be increased.Methods: Eighty participants in twenty-seven maternity units were interviewed after the first intervention sequence of the programme. A content analysis using a priori coding was performed in order to relate results to the anticipated outcomes of three basic interventions: self-assessment, peer review and written feedback, and agreement for change.Results: The self-assessment procedure was valuable and served as a useful tool for elucidating strengths and weaknesses and identifying areas for improvement for a safer delivery in maternity units. The peer-review intervention was appreciated, despite it being of less value when considering the contribution to explicit outcome effects (i.e. new input to team mental models and new suggestions for actions). The feedback report and the mutual agreement on measures for improvements reached when signing the contract seemed exert positive pressures for change.Conclusions: Our findings are in line with several studies stressing the importance of self-evaluation by encouraging a thorough review of objectives, practices and outcomes for the continuous improvement of an organisation. Even though effects of the peer review were limited, feedback from peers, or other change agents involved, and the support that a clear and well-structured action plan can provide are considered to be two important complements to future self-assessment procedures related to patient safety improvement.
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| 8. |
- Parigi, Sara M., et al.
(författare)
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Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- A common helper-like innate lymphoid precursor (CHILP) restricted to the innate lymphoid cells (ILC) lineage has been recently characterized. While specific requirements of transcription factors for CHILPs development has been partially described, their ability to sense cytokines and react to peripheral inflammation remains unaddressed. Here, we found that systemic increase in Flt3L levels correlated with the expansion of Lineage (Lin)(neg)alpha 4 beta 7(+) precursors in the adult murine bone marrow. Expanded Lin(neg)alpha 4 beta 7(+) precursors were bona fide CHILPs as seen by their ability to differentiate into all helper ILCs subsets but cNK in vivo. Interestingly, Flt3L-expanded CHILPs transferred into lymphopenic mice preferentially reconstituted the small intestine. While we did not observe changes in serum Flt3L during DSS-induced colitis in mice or plasma from inflammatory bowel disease (IBD) patients, elevated Flt3L levels were detected in acute malaria patients. Interestingly, while CHILP numbers were stable during the course of DSS-induced colitis, they expanded following increased serum Flt3L levels in malaria-infected mice, hence suggesting a role of the Flt3L-ILC axis in malaria. Collectively, our results indicate that Flt3L expands CHILPs in the bone marrow, which might be associated with specific inflammatory conditions.
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