| 1. |
- Axelsson, Susanne, et al.
(författare)
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A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex
- 2020
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Ingår i: BMC Immunology. - : BioMed Central (BMC). - 1471-2172. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of anti-B cell based therapies in immune-mediated diseases targeting general B cell markers or molecules important for B cell function has increased the clinical needs of monitoring B cell subpopulations.RESULTS: We analyzed the expression profile of cell surface markers CD86 and B and T lymphocyte attenuator (BTLA) in B cell subtypes using flow cytometry, including naïve, transitional, switched memory, non-switched memory and double-negative memory B cells and plasmablasts, and investigated the dependence of age and sex in a healthy adult blood donor population. The switched memory B cell subtype displayed a divergent expression of the markers, with increased CD86 and decreased BTLA as compared to non-switched and double negative memory cells, as well as compared to naïve B cells. Plasmablasts expressed highly increased CD86 compared to all other subtypes and a decreased expression of BTLA compared to naïve cells, but still higher compared to the memory cell populations. Transitional B cells had CD86 and BTLA expression similar to the other naïve cells.CONCLUSIONS: We show divergent expression of CD86 and BTLA in memory cells and plasmablasts compared to naïve B cells independent of age and sex. Furthermore, a similarly divergent difference of expression pattern was seen between the memory cell subtypes, altogether indicating that the combination of CD86 and BTLA might be markers for a permissive activation state. We suggest the combination of CD86 and BTLA expression on B cell subtypes as a potentially important tool in monitoring the status of B cell subtypes before and after treatments influencing the B cell compartment.
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| 2. |
- Berglund, Martin, 1979, et al.
(författare)
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Gender dependent importance of IRAK-1 in dextran sulfate sodium induced colitis
- 2009
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Ingår i: Cellular Immunology. - : Elsevier BV. - 1090-2163 .- 0008-8749. ; 259:1, s. 27-32
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptor (TLR) signaling is important for the induction of pro-inflammatory cytokines and interferon (IFN)-inducible genes in response to bacterial and viral challenge. Interleukin-1 receptor-associated kinase-1 (IRAK-1) is a signaling kinase situated downstream of the adapter protein myeloid differentiation factor 88 (MyD88) in the TLR intracellular signaling cascade and is required for normal signal transduction through this pathway. We investigated the importance of IRAK-1 in intestinal inflammation by using the dextran sulfate sodium (DSS)-colitis model. We show that IRAK-1 deficient mice are protected against systemic signs of inflammation, i.e., weight loss and spleen enlargement compared to wild-type controls irrespective of gender. However, IRAK-1(-/y) males but not IRAK-1(-/-) females display significant protection against colitis and thymic atrophy compared to wild-type mice. Our results indicate a gender specific effect of IRAK-1 in the DSS-induced colitis, an interesting finding since the Irak-1 gene is located on the X-chromosome and several inflammatory diseases have a gender dependent incidence.
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| 3. |
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| 4. |
- Berglund, Martin, et al.
(författare)
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IL-1 receptor-associated kinase M downregulates DSS-induced colitis
- 2010
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 16:10, s. 1778-1786
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced model of colitis. Methods: IRAK-M-competent and -incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T-cell transcription factors. Results: At day 7 IRAK-M-deficient mice display a reduced total body weight (77.1 +/- 2.1 versus 88.5 +/- 2.0, *P=0.002) and an increased macroscopical (2.7 +/- 0.2 versus 1.6 +/- 0.1, *P 0.002) and histopathological (6.0 +/- 0 versus 3.3 +/- 60.5, *P < 0.001) colon score compared to wildtype mice. Furthermore, IRAK-M-deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 +/- 13.5 versus 12.8 +/- 2.0 pg/mL, *P = 0.010) in plasma. Conclusions: This is the first report examining the role of IRAK-M in colitis. We find that IRAK-M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK-M might be a target for future interventional therapies. (Inflamm Bowel Dis 2010; 16: 1778-1786)
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| 5. |
- Berglund, Martin, 1979, et al.
(författare)
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Toll-like receptor cross-hyporesponsiveness is functional in interleukin-1-receptor-associated kinase-1 (IRAK-1)-deficient macrophages : differential role played by IRAK-1 in regulation of tumour necrosis factor and interleukin-10 production
- 2008
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 67:5, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- Signalling downstream Toll-like receptors (TLR) is regulated at several levels in order to activate the immune response and prevent excessive inflammation. Altered intracellular signalling may be one reason that repeated stimulation of various TLRs results in hyporesponsiveness and cross-tolerance. We report that TLR cross-tolerance is inducible in the absence of interleukin-1 receptor-associated kinase-1 (IRAK-1) in peritoneal macrophages. Similar to wild-type macrophages, IRAK-1-deficient macrophages respond with decreased tumour necrosis factor (TNF) production to a secondary TLR stimulation, but in opposite to IRAK-1(+/+), IRAK-1(-/-) macrophages display increased interleukin (IL)-10 production at TLR restimulation. IRAK-1-deficient peritoneal macrophages have a defective TNF and IL-10 production in response to lipoteichoic acid stimulation as well as a defective IL-10-but a normal TNF production in response to high concentration of lipopolysaccharide. Our results demonstrate that IRAK-1 is not necessary for induction of TLR cross-tolerance as judged by TNF production.
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| 6. |
- Bjursten, Malin, 1976, et al.
(författare)
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Enhanced pro-inflammatory cytokine production in Galphai2-deficient mice on colitis prone and colitis resistant 129Sv genetic backgrounds.
- 2004
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Ingår i: Cellular immunology. - : Elsevier BV. - 0008-8749. ; 228:2, s. 77-80
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient in G-protein subunit alphai2 develop colitis closely resembling human ulcerative colitis when raised on 129SvEv background. When backcrossing the Galphai2-deficiency into a 129SvJBom genetic background, surprisingly, mice did not develop colitis. In vitro stimulation of splenocytes with formalin-killed Staphylococcus aureus resulted in significantly increased production of interleukin-1beta, tumor necrosis factor, and interleukin-12p40 in Galphai2(-/-) as compared to control mice. The enhanced production of pro-inflammatory cytokines was seen in colitis prone as well as in colitis resistant genetic background. A similar outcome was seen upon stimulation with toxic shock syndrome toxin-1, a T cell superantigen, except that Galphai2(-/-) colitis resistant 129SvJBom splenocytes did not show increased production of IL-12p40 as compared to their controls.
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| 7. |
- Dolatkhah, Mats
(författare)
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Läsfrämjande i pedagogisk verksamhet
- 2015
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Annan publikation (refereegranskat)abstract
- Flera institutioner i samhället arbetar på olika sätt med barns och ungas läsning. Dels handlar det om att barn och unga behöver utveckla läsförmågan för att kunna delta i utbildning, arbete och samhällsliv, dels eftersträvas ofta att utveckla läsintressen och läsvanor. På politisk nivå sätts läsandet i samband med såväl individuella som samhälleliga värden och ses ofta som en tillgång för demokratin (se t.ex. Litteraturutredningen 2012a, och Proposition 2013/14:3). I artikeln tas upp en omfattande forskning om läsning som kan vara av intresse för detta arbete.
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| 8. |
- Günaltay, Sezin, 1986-, et al.
(författare)
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Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis
- 2014
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Ingår i: World Journal of Gastroenterology. - : WJG Press. - 1007-9327 .- 2219-2840. ; 20:34, s. 12249-12259
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
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| 9. |
- Günaltay, Sezin, 1986-
(författare)
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Dysregulated mucosal immune responses in microscopic colitis patients
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC) is a common cause of chronic watery diarrhea. The diagnosis relies on typical histopathological changes observed upon microscopic examination. The studies in this thesis investigated innate and adaptive immune responses in the colonic mucosa of MC patients, also comparing patients with active disease (CC and LC) and histopathologically in remission (CC/LC-HR). We first analyzed expression of interleukin-1/Toll-like receptor (IL-1/TLR) signaling regulators in MC patients (Paper I). Our results showed enhanced IRAK-M, microRNA-146a, -155 and -21 expressions, whereas IL-37 gene expression was reduced in CC and LC patients as compared to non-inflamed controls. These results suggest different pathophysiological mechanisms in MC patients. The mixed inflammatory cell infiltrations seen in the lamina propria of MC patients might be a result of dysregulated expression of chemotactic mediators. In Paper II, we showed that MC patients display mainly an increased expression of chemokines and chemokine receptors in active disease as compared to noninflamed controls. In Paper III, we examined if the decreased IL-37 expression seen in Paper I could mediate the upregulation of chemokines seen in Paper II. We showed that a relatively small reduction in the ability of epithelial cells to produce IL-37 results in mainly increased chemokine expressions in a pattern similar to the findings in Paper II. In order to understand the nature of infiltrating T cells commonly observed in MC patients, we analyzed the T cell receptor (TCR) β chains in colonic biopsies of MC patients (Paper IV). Our results showed significant differences in TCRβ repertoire, which suggests selectively expanded T cell clones in active MC and histopathologically in remission patients. Altogether, these results i) increase the knowledge of MC pathogenesis by showing changes in TLR signaling regulators, enhanced chemokine and their receptor expressions involved in a mixed immune cell infiltrations and selectively expanded T cell clones in CC and LC patients, as well as in histopathological remission ii) might potentially increase the possibility of more target-specific therapies based on IL-37 induction, chemokines or chemokine receptor inhibitions, or hindering T cell infiltration according to TCR clonality.
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| 10. |
- Gunaltay, Sezin, 1986-, et al.
(författare)
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Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
- 2015
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861.
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Tidskriftsartikel (refereegranskat)abstract
- Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.
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| 11. |
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| 12. |
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| 13. |
- Gunaltay, Sezin, 1986-, et al.
(författare)
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Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
- 2017
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 23:6, s. 932-945
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.
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| 14. |
- Günaltay, Sezin, 1986-, et al.
(författare)
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Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial Cells
- 2017
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Ingår i: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 62:5, s. 1204-1215
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. Previously, we showed enhanced chemokine productions in microscopic colitis patients, indicating dysregulated immune cell chemotaxis in the immunopathogenesis. We also showed decreased mRNA of IL-37, mainly regarded as an anti-inflammatory cytokine, in the colonic mucosa of these patients, potentially an important factor for the chronicity of the colitis. Our aim in this study was to understand the possible role of IL-37 in chemokine production using a cell line model.Methods: A colon epithelial cell line, T84, was stimulated with the TLR5 ligand flagellin. IL-37 protein production was reduced 20% using the CRISPR/Cas9 system, and the changes in chemokine mRNA and protein expressions were compared to cells transfected with empty plasmid.Results: The 20% reduction in IL-37 protein levels spontaneously increased CCL5, CXCL8, CXCL10, and CXCL11 mRNA and protein expressions. CCL2 mRNA and protein levels were enhanced upon TLR5 stimulation. CCL3, CCL20, and CX3CL1 mRNA expressions were increased either spontaneously or following TLR5 stimulation, whereas CCL4 and CCL22 mRNA expressions were significantly decreased.Conclusions: Even a minor decrease in the ability of colon epithelial cells to produce IL-37 results in altered chemokine expression, mainly an increase in the production of several chemokines. Our results indicate that a decreased IL-37 expression by colon epithelial cells may be an important factor for increasing the recruitment of immune cells and subsequently developing microscopic colitis.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Hultgren, Olof H., 1970, et al.
(författare)
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Serum interleukin-1 receptor antagonist is an early indicator of colitis onset in Galphai2-deficient mice.
- 2006
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Ingår i: World journal of gastroenterology : WJG. - 1007-9327. ; 12:4, s. 621-4
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the serum concentration of IL-1beta, IL-1 receptor antagonist (IL-1Ra) and IL-18 in Galphai2-deficient mice at the age of 6 (healthy), 12 (pre-colitic) and 24 wk (colitic) and in healthy control mice. METHODS: At the time of killing, serum samples were collected and IL-1beta, IL-1Ra and IL-18 levels were measured using enzyme-linked immunosorbent assays. RESULTS: Serum concentration of IL-1Ra was significantly increased in pre-colitic (median: 524 ng/L; P=0.02) and colitic (450 ng/L; P=0.01), but not in healthy (196 ng/L) Galphai2-deficient mice as compared with controls (217 ng/L). Serum concentrations of IL-1beta did not differ between Galphai2-deficient mice and their controls, irrespective of age, IL-18 was significantly increased in colitic, but not in pre-colitic mice compared with controls (510 ng/L vs 190 ng/L; P=0.05). CONCLUSION: The increased serum concentrations of IL-18 and IL-1Ra in established diseases are suggested as markers of ongoing colitis. Interestingly, the significantly increased serum concentration of IL-1Ra in pre-colitic mice is found to be an early marker of disease progression.
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| 19. |
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| 20. |
- Kumawat, Ashok Kumar, et al.
(författare)
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An in vitro model for analysis of the impact of the colonic milieu in collagenous colitis patients on peripheral T lymphocyte activation and differentiation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Soluble factors released by intestinal mucosal cells contribute to immune homeostasis in the gut. This is the first study to investigate the role of soluble factors from the intestinal mucosa of collagenous colitis (CC) patients in the regulation of effector T cells using a novel system that mimics the in vivo exposure of newly recruited peripheral blood T cells to soluble factors derived from the colonic milieu of normal individuals and inflamed CC patient mucosa.Methods: Denuded biopsies (DNB) and isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients and non-inflamed controls were cultured to collect conditioned medium (CM). Enriched peripheral blood CD4+ T cells from healthy donors were polyclonally activated in the absence or presence of CM from CC patients and controls. Proliferation, as well as secretion of IL-1β IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α was analysed the latter with Luminex® analysis.Results: Peripheral CD4+ T cells exposed to CM from the colonic mucosa demonstrated reduced proliferation. This inhibition was less pronounced with DNB-CM derived from CC patients compared to non-inflamed control mucosa. In contrast, LPMC-CM from non-inflamed controls inhibited T-cell proliferation less than LPMC-CM from CC patients. Both DNB-CM and LPMC-CM from CC patients induced more or less increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6 and TNF-α as well as the anti-inflammatory cytokines IL-4 and IL-10 from peripheral CD4+ T cells compared to non-inflamed controls. In contrast, IL-1β production by peripheral T cells showed mixed results – it was either increased or reduced in the presence of both DNB and LPMC-CM from CC patients compared to noninflamed controls with different blood donors and different concentrations.Conclusion: Our preliminary data indicates reduced inhibition of proliferation of peripheral CD4+ T cells in the presence of mucosa-derived soluble factors from CC patients compared to controls. In addition, increased production of both inflammatory and anti-inflammatory cytokines by peripheral CD4+ T cells was recorded in the presence of soluble factors from the colonic mucosa of CC patients compared to controls. This model can be valuable in evaluating the effect(s) of existing and new drugs on T cell differentiation in the intestinal mucosa.
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| 21. |
- Kumawat, Ashok Kumar, 1982-, et al.
(författare)
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An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells : Enhanced Production of IL-17A and IL-10 from Peripheral CD4(+) T Cells
- 2014
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Ingår i: Mediators of Inflammation. - New York, USA : Hindawi Publishing Corporation. - 0962-9351 .- 1466-1861.
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Tidskriftsartikel (refereegranskat)abstract
- Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4(+) T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-gamma, IL-17A, IL-6, and IL-1 beta and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4(+) T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro-and anti-inflammatory cytokines.
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| 22. |
- Lushnikova, Alexandra, et al.
(författare)
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Altered levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls
- 2021
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Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 206:Suppl.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disorder. MC patients have a lower risk of developing colorectal cancer (CRC) than ulcerative colitis (UC) patients. We hypothesize that the immune response in MC is geared more towards immune surveillance of tumor cells than that of UC, which instead contributes to inflammation-associated CRC.Methods: Using Luminex, protein levels of 14 immune checkpoints (TIM-3, CD28, CD137, CD27, CD152, HVEM, IDO, LAG-3, BTLA, GITR, CD80, PD-1, PD-L1, PD-L2) in protein lysates from colon biopsies (controls, n = 9; diarrhea controls, n = 7; LC, n = 14; CC, n = 15; UC, n = 17) were analyzed. Soluble checkpoints were analyzed in serum (23 controls, 17 LC, 36 CC and 2 UC).Results: In patients with active LC and CC, CD137, IDO, and CD80 levels were increased compared with one or both control groups. CD152 and PD-1 levels were increased in patients with active CC compared with both control groups. In patients with active UC, levels of CD137, CD152, BTLA, PD-1, and PD-L2 were increased compared with both control groups, IDO levels were increased compared with controls, and CD80 levels were raised compared with diarrhea controls.In sera, CD27, IDO, CD80, PD-1, and PD-L2 levels were decreased in LC patients compared to controls.Conclusions: Increased levels of immune checkpoint molecules in colon biopsies from UC and MC patients are likely a sign of inflammation and may indicate what kind of homeostatic feed-back mechanisms are active to balance inflammation. Lowered concentrations of soluble immune checkpoint molecules in sera from patients with LC indicate a different level of homeostatic balance systemically in LC patients versus controls.
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| 23. |
- Lushnikova, Alexandra, et al.
(författare)
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Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls
- 2021
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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media S.A.. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.
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| 24. |
- Rydsjö, Kerstin, et al.
(författare)
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Det samtida barnbiblioteket : ett bibliotek i barnens tjänst
- 2010
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Ingår i: Stockholms stadsbibliotekets skriftserie;16. - : Regionbiblioteket Stockholm. - 9789197849043 ; , s. 271-286
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- En sammanfattande analys av antologin "Barnet, platsen tiden: teorier och forskning i barnbibliotekets omvärld". Redaktörerna analyserar bidrag i antologin från forskningsfält som på olika sätt har betydelse för barnbibliotket.
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| 25. |
- Öhman, Lena, 1967, et al.
(författare)
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Acellular Bordetella pertussis vaccine enhances mucosal interleukin-10 production, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2-deficient mice.
- 2005
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 141:1, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient for the inhibitory G protein subunit alpha2 (Galphai2(-/-)) spontaneously develop a progressive inflammatory bowel disease resembling ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior to onset of colitis, which is further augmented after the onset of disease. The present study was performed to investigate whether the Galphai2(-/-) mice were able to down-regulate the Th1-dominated inflammatory mucosal immune response and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish the severity of colitis following treatment with acellular Bordetella pertussis vaccine. The acellular vaccine against B. pertussis, the causative agent of whooping cough, has been demonstrated to induce a Th2-mediated response in both man and mice. We therefore treated Galphai2(-/-) mice intraperitoneally with a three-component acellular B. pertussis vaccine. The treated Galphai2(-/-) mice showed significantly increased interleukin (IL)-10 production in intestinal tissue, associated with significantly reduced colitis and decreased mortality, compared to untreated Galphai2(-/-) mice. The attenuation of colitis in Galphai2(-/-) mice was due, at least partly, to the B. pertussis surface antigen filamentous haemagglutinin (FHA), which almost completely inhibited proliferation of CD4(+) T cells and stimulated apoptosis of activated CD4(+) T helper 1 cells. In conclusion, the three-component acellular B. pertussis vaccine containing filamentous haemagglutinin increases the production of IL-10 in the intestinal mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2(-/-) mice.
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| 26. |
- Adolfsson, Per I., et al.
(författare)
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Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.
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| 27. |
- Agmon-Levin, Nancy, et al.
(författare)
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International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:1, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
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| 28. |
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| 29. |
- Ahmed, Haseeb, et al.
(författare)
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Animal welfare efforts and farm economic outcomes: Evidence from Swedish beef production
- 2023
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Ingår i: Agricultural and Resource Economics Review. - 1068-2805. ; 52, s. 498-519
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Tidskriftsartikel (refereegranskat)abstract
- We estimate the relationship between farm animal welfare (FAW) efforts taken by beef farmers and the economic performance of beef farms by using farm accounting data from the Swedish Farm Economic Survey matched with survey data on farm management practices. To this end, we perform a two-step analysis. First, an item response theory (IRT) model estimates the latent FAW effort on farms. FAW effort likely depends on a host of complementary FAW-improving strategies, and the IRT model combines the considered strategies into a unidimensional scale. We take this to represent on-farm FAW effort. Second, we use instrumental variable regressions to estimate the relationship between FAW effort and multiple measures of farm economic performance. We find that higher FAW effort scores have no effect on margins and costs. However, higher FAW effort scores are associated with lower farm sales. Findings suggest that policies (such as targeted label for high FAW) that increase farm revenue as well as incentivize the uptake of FAW-improvement practices may be able to compensate farmers for their FAW effort.
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| 30. |
- Ahmed, Haseeb, et al.
(författare)
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Assessing Animal Welfare and Farm Profitability in Cow-Calf Operations with Stochastic Partial Budgeting
- 2021
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Simple SummaryThe increased consumer demand for high levels of farm animal welfare (FAW) have prompted debates about the costs of achieving higher FAW. Yet, little is known about the economic consequences of improvements in FAW, especially in cow-calf operations. This study contributes to the literature by investigating the relationship between farm profitability and improved FAW measure in terms of increased space allowance in Swedish cow-calf operations. We found that a 0.5 m(2) increase in space allowance per calf (achieved by a corresponding reduction of herd size) was associated with a 6.9 to 18.7% reduction in farm-level contribution margins in the short term. Our results suggest that FAW improvements can be costly for farms and these costs should be considered while taking policy decisions regarding improvements in FAW standards.The societal demand for good farm animal welfare (FAW) has increased over time. Yet, very little is known about the economic consequences of improvements in FAW in cow-calf operations. This study investigates on-farm economic consequences of improved FAW measures in cow-calf operations. It uses a stochastic partial budgeting approach to examine the relationship between contribution margins and improvements in FAW in terms of increased space allowance for a typical Swedish cow-calf operation, as compared to current practices. In the current practice, a cow should be given at least 5 m(2) and the calf 2.2 m(2). We found that a 0.5 m(2) increase in space allowance per calf (achieved by a corresponding reduction of herd size) was associated with a 6.9 to 18.7% reduction in contribution margins in the short term. Our analysis does not include possible indirect gains like decrease in disease incidence and enhanced non-use or 'soft' values associated with increased FAW. However, our analysis indicates that high FAW standards can be costly and careful cost-benefit analysis should be a part of decision-making processes regarding FAW standards. Our results also suggest a need for government support payments and/or the development of market mechanisms to stimulate farmers to continue producing livestock-based foods with high FAW.
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| 31. |
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| 32. |
- Ahmed, Haseeb, et al.
(författare)
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Assessing economic consequences of improved animal welfare in Swedish cattle fattening operations using a stochastic partial budgeting approach
- 2020
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Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 232
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Tidskriftsartikel (refereegranskat)abstract
- There is an increased concern among many stakeholders in society that livestock production systems provide a low-quality life to the animals and therefore advocate improved farm animal welfare (FAW). On the other hand, producers are concerned that stricter welfare regulations would decrease their profits and hence their competitiveness. Given the relevance of the debate surrounding FAW especially in Sweden, and the lack of studies related to the beef sector, this study examined the impact of changes in FAW practices on economic performance of Swedish beef fattening operations. We modelled a herd of 50 cattle of either beef or dairy breed reared for meat production to examine the impact of increased space allowance, including a corresponding decrease in herd size, and increased forage-to-concentrate (FC) ratio. We found that a 1-m(2)/animal increase in space allowance was associated with a decrease of 18.9 and 10.8% in short-run, per animal profits in beef and dairy breeds, respectively. Sensitivity analysis suggested that an increase in weight gain and short-run loss in herd size due to increased space allowance were the most important factors. We estimated that an increase in the FC ratio from 40:60 to 65:35 was associated with a reduction in per animal profits of about 21 to 34% in beef breeds and 17 to 53% in dairy breeds, respectively. Sensitivity analysis indicated that reduced growth due to increased FC ratio was the most important factor. Our results suggest that an increase in space allowance or FC ratio in Swedish beef fattening operations may reduce farm profitability. They also imply that consequences of any policy instrument should be carefully examined to reach the goal of improved FAW along with improved profitability and sustainability for the farmer.
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| 33. |
- Ahmed, Haseeb, et al.
(författare)
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Costs and benefits of good animal welfare - for animals, farmers and society
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Society’s demand for good animal welfare has led to discussions about the costs of achieving and maintaining one. This is relevant to Swedish animalbased food production, because producers in Sweden in many respects have stricter requirements than farmers in other countries. They therefore face competition from imported foods produced under less strict animal welfare regulations. At the same time, good animal welfare can have a value in itself and can provide benefits for animals, farmers and society.
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| 34. |
- Ahmed, Haseeb, et al.
(författare)
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Kostnader och vinster med gott djurskydd : för djur, lantbrukare och samhälle
- 2022
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Annan publikation (populärvet., debatt m.m.)abstract
- Samhällets krav på god djurvälfärd har lett till diskussioner om kostnaderna för att uppnå och upprätthålla en sådan. Detta är relevant för svensk djurbaserad livsmedelsproduktion, eftersom producenter i Sverige i många avseenden har hårdare krav än i andra länder. De möter därför konkurrens från importerade livsmedel som producerats med mindre strikta djurskyddsbestämmelser. Samtidigt kan gott djurskydd ha ett värde i sig och ge fördelar för djur, lantbrukare och samhälle.
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| 35. |
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| 36. |
- Alanärä, Anders, et al.
(författare)
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Utsättning av djur för jakt och fiske
- 2021
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Bok (populärvet., debatt m.m.)abstract
- SLUs vetenskapliga råd för djurskydd har fått i uppdrag av Jordbruksverket att sammanställa aktuell forskning kring utsättning av djur för jakt och fiske samt att belysa eventuella kunskapsluckor på området. Uppdraget omfattar gräsand, rapphöna, fasan och laxfiskar. Bruket att föda upp fåglar och fiskar för utsättning i syfte att gynna jakt och fiske ifrågasätts inte sällan av etiska skäl, men den diskussionen ligger utanför fokus för denna rapport. Utsättning av fågel och fisk är en antropogen verksamhet som, till skillnad från många andra typer av mänsklig påverkan, syftar till att gynna arterna i fråga. Det kan handla om naturvårdsinsatser, att återinföra försvunna arter eller att på andra sätt berika ekosystemet, inte sällan med ökade möjligheter till jakt eller fiske som slutändamål. Ofta förbereds och åtföljs utsättningar av habitatförbättrande åtgärder som inte endast gynnar de utsatta individerna och deras artfränder, utan även har positiva konsekvenser för biologisk mångfald och ekosystemet i stort. I utarbetandet av regelverket knutet till utsättning av fågel och fisk är det viktigt att även beakta de positiva föresatserna och de konsekvenser som verksamheten kan medföra. Annars riskerar man att engagemang och incitament förloras, till men för biologisk mångfald och en rik och levande landsbygd.
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| 37. |
- Algers, Bo, et al.
(författare)
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EU i otakt med sin egen lagstiftning
- 2014
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Ingår i: Svensk Veterinärtidning. - 0346-2250. ; 66, s. 41-44
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 38. |
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| 39. |
- Algers, Bo, et al.
(författare)
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Riskbedömning av djurvälfärd
- 2010
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Ingår i: Svensk Veterinärtidning. - 0346-2250. ; 62, s. 17-19
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Almqvist, Viktor, et al.
(författare)
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Evaluating remote post-mortem veterinary meat inspections on pig carcasses using pre-recorded video material
- 2023
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Ingår i: Acta Veterinaria Scandinavica. - 0044-605X .- 1751-0147. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOfficial meat inspections at small-scale slaughterhouses and game-handling establishments in geographically remote areas place a heavy burden on the meat-producing food business operators. By performing meat inspections remotely using live-streamed video, instead of on-site, the official control could meet the goals of sustainability, resilience and logistics. We investigated the agreement between the two approaches at pig slaughter. Two official veterinarians (OVs) inspected 400 pig carcasses at a Swedish slaughterhouse, with each pig being inspected on site by one OV and remotely by the other. After a period of 3 to 6 months, video recordings of the remote inspections were assessed again by the same OVs, thus enabling direct comparisons of previous on-site inspections and renewed video-based inspections within the same OV.ResultsAgreement across 22 finding codes was generally very high for both OVs. In all but one case (whether to fully condemn a carcass), for both OVs, Prevalence-Adjusted Bias-Adjusted kappa was well above 0.8, indicating 'almost perfect agreement'.ConclusionsThis study supports earlier findings that reliable post-mortem inspections can be performed using video, and indicates higher agreement between remote and on-site inspections if the same OV performs both.
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| 46. |
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| 47. |
- Almqvist, Viktor, et al.
(författare)
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Reliability of remote post-mortem veterinary meat inspections in pigs using augmented-reality live-stream video software
- 2021
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Ingår i: Food Control. - : Elsevier BV. - 0956-7135 .- 1873-7129. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- Official meat inspections at remotely situated, small-scale slaughter houses and game handlings establishments fare associated with a relatively high cost of official control per inspected animal. By performing veterinary meat inspections via live-streamed video, this cost could be lowered. We aimed to evaluate how veterinary meat inspections at slaughter can be conducted remotely with the help of a camera-equipped non-veterinary technician on site. Specialized software and augmented reality technology were used. The remote inspection was compared to standard on-site veterinary meat inspection at a large-scale slaughter plant for pigs in Sweden during 2019. The remote and on-site inspectors recorded findings in 400 carcasses and organs arrested for further inspection. The comparison was based primarily on percentage agreement, Cohen?s kappa and prevalence- and bias-adjusted kappa (PABAK) as measures of agreement and reliability. The remote method was shown to display a high level of agreement for clear, easily distinguished findings (e.g. tail lesions, with an agreement of 92.3%, Cohen?s kappa of 0.77 and PABAK of 0.85). For more vague findings and subjective decisions, the performance was slightly lower (e.g. whether or not to condemn a carcass completely, with agreement 75.2%, Cohen?s kappa 0.32 and PABAK 0.50). Remote inspection appears to constitute a viable alternative for post-mortem meat inspection in pigs, given a sufficiently standardized method of inspection and sufficient inspection times. The performance of remote inspection probably depends on which persons use the method.
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| 48. |
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| 49. |
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| 50. |
- Ambite, Ines, et al.
(författare)
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Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae
- 2019
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 15:6, s. 1007671-1007671
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Tidskriftsartikel (refereegranskat)abstract
- Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E. coli 83972pap stably reprogrammed host gene expression, by activating an acute pyelonephritis-associated, IRF7-dependent gene network. The PapG protein was internalized by human kidney cells and served as a transcriptional agonist of IRF-7, IFN-β and MYC, suggesting direct involvement of the fimbrial adhesin in this process. IRF-7 was further identified as a potent upstream regulator (-log (p-value) = 61), consistent with the effects in inoculated patients. In contrast, E. coli 83972fim transiently attenuated overall gene expression in human hosts, enhancing the effects of E. coli 83972. The inhibition of RNA processing and ribosomal assembly indicated a homeostatic rather than a pathogenic end-point. In parallel, the expression of specific ion channels and neuropeptide gene networks was transiently enhanced, in a FimH-dependent manner. The studies were performed to establish protective asymptomatic bacteriuria in human hosts and the reconstituted E. coli 83972 variants were developed to improve bacterial fitness for the human urinary tract. Unexpectedly, P fimbriae were able to drive a disease response, suggesting that like oncogene addiction in cancer, pathogens may be addicted to single super-virulence factors.
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