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- Dige, A., et al.
(författare)
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Effects of Anti-TNFα Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease
- 2018
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2018
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Tidskriftsartikel (refereegranskat)abstract
- T helper 17 (Th17) cells produce interleukin (IL) 17-A. In addition, Th17 cells produce IL-21 and IL-22. Th17 cells have a disease-promoting role in Crohn’s disease (CD). We investigated the effects of anti-TNFα treatment on mucosal gene expression (qPCR) of IL-17A, IL-21, and IL-22 as well as on the frequency of lamina propria (LP) T cell subsets producing these cytokines (flow cytometry) in 12 active CD patients before and after 4 weeks of anti-TNFα treatment with adalimumab. At baseline, in inflamed mucosa we found increased gene expression of IL-17A and IL-22 but not IL-21 when compared to noninflamed mucosa. There were increased frequencies of IL-21-producing LP T cells but no differences in the frequencies of IL-17A- or IL-22-producing LP T cells when comparing inflamed versus noninflamed mucosa at baseline. There were no changes in the mucosal gene expression of IL-17A, IL-21, and IL-22 or the frequencies of IL-17A-, IL-21- and IL-22-producing LP T cell subsets between baseline and following 4 weeks of adalimumab initiation. Our results do not support the hypothesis that anti-TNFα treatment has an early effect on the mucosal levels of IL-17A, IL-21, and IL-22 or LP T cell production of these cytokines in CD.
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| 3. |
- Dige, A., et al.
(författare)
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Reduced numbers of mucosal DRint macrophages and increased numbers of CD103(+) dendritic cells during anti-TNF-alpha treatment in patients with Crohn's disease
- 2016
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:6, s. 692-699
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Tidskriftsartikel (refereegranskat)abstract
- Objective Anti-TNF-alpha treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-alpha antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood. Material and methods Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DRint and CD14 (+) DRhi MQs, CD141(+), CD141(-) and CD103(+ )DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry. Results At baseline, we observed higher numbers of DRint MQs and lower numbers of CD103(+ )DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 x 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DRint MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+ )DCs increased [9-20 x 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4. Conclusions In CD, mucosal inflammation is associated with high numbers of DRint MQs and low numbers of CD103(+ )DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-alpha treatment. These results suggest that DRint MQs play a pivotal role in CD inflammation.
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| 4. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Macrophage and dendritic cell subsets in IBD: ALDH cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation
- 2016
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1935-3456 .- 1935-3456 .- 1933-0219. ; 9:1, s. 171-182
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Tidskriftsartikel (refereegranskat)abstract
- Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers were unchanged. However, CD103+ DCs, including CD141+CD103+ and CD1c+CD103+ DCs, were reduced in inflamed intestine. In MLNs, two CD14- DC populations were identified: CD11cintHLADRhi and CD11chiHLADRint cells. A marked increase of CD11chiHLADRint DC, particularly DRintCD1c+ DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.
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| 5. |
- Bak, Nina Friis, et al.
(författare)
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High-dose vitamin D3 supplementation decreases the number of colonic CD103+ dendritic cells in healthy subjects.
- 2018
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 57:7, s. 2607-2619
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103+DCs of high-dose vitamin D3 treatment in healthy subjects.Ten healthy subjects received a total of 480,000IU oral vitamin D3 over 15days and colonic biopsies were obtained before and after intervention by endoscopy. Lamina propria mononuclear cells (LPMCs) were isolated from the biopsies, stained with DC surface markers and analysed with flow cytometry. Snap-frozen biopsies were analysed with qPCR for DC and regulatory T cell-related genes.No hypercalcemia or other adverse events occurred in the test subjects. Vitamin D decreased the number of CD103+ DCs among LPMCs (p=0.006). Furthermore, vitamin D induced mRNA expression of TGF-β (p=0.048), TNF-α (p=0.006) and PD-L1 (p=0.02) and tended to induce IL-10 expression (p=0.06). Multivariate factor analysis discriminated between pre- and post-vitamin D supplementation with a combined increased qPCR expression of PD1, PD-L1, TGF-β, IL-10, CD80, CD86, FOXP3, NFATc2 and cathelicidin.High-dose vitamin D supplementation is well tolerated by healthy subjects and has a direct effect on the CD103+ DCs, local cytokine and surface marker mRNA expression in the colonic mucosa, suggestive of a shift towards a more tolerogenic milieu.
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