Activated Mucosal-associated Invariant T Cells Have a Pathogenic Role in a Murine Model of Inflammatory Bowel Disease
| Autor: | Yusuke Yasutomi, Ryuichi Okamoto, Keiichi Haga, Ayako Makiyama, Goh Murayama, Asako Chiba, Sachiko Miyake, Mamoru Watanabe, Taiga Kuga, Takashi Nagaishi, Akihito Nagahara |
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| Rok vydání: | 2022 |
| Předmět: |
medicine.medical_treatment
RC799-869 i6-FP isobutyryl 6-formyl pterin Mucosal associated invariant T cell MAIT Cell Inflammatory bowel disease Mucosal-Associated Invariant T Cells Pathogenesis Mice NIH National Institutes of Health CD Crohn’s disease medicine Animals Humans Mucosal Immunity IFN interferon LPL lamina propria lymphocyte Colitis MR1 major histocompatibility complex-related molecule 1 Original Research TNF tumor necrosis factor Intestinal permeability IBD inflammatory bowel disease Hepatology TCR T cell receptor business.industry Inflammatory Bowel Disease RL-7-Me 7-methyl-8-D-ribityllumazine Gastroenterology iNKT invariant natural killer T cells Diseases of the digestive system. Gastroenterology Inflammatory Bowel Diseases medicine.disease Gut Integrity WT wild-type Ulcerative colitis IL interleukin Mice Inbred C57BL Disease Models Animal UC ulcerative colitis Cytokine PBMC peripheral blood mononuclear cells Immunology Colitis Ulcerative DAI disease activity index FITC fluorescein isothiocyanate MAIT cells mucosal-associated invariant T cells Cell activation business |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 1, Pp 81-93 (2022) |
| ISSN: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2021.08.018 |
| Popis: | Background & Aims Mucosal-associated invariant T (MAIT) cells are innate-like T cells restricted by major histocompatibility complex-related molecule 1 (MR1) and express a semi-invariant T cell receptor. Previously, we reported the activation status of circulating MAIT cells in patients with ulcerative colitis (UC) was associated with disease activity and that these cells had infiltrated the inflamed colonic mucosa. These findings suggest MAIT cells are involved in the pathogenesis of inflammatory bowel disease. We investigated the role of MAIT cells in the pathogenesis of colitis by using MR1−/− mice lacking MAIT cells and a synthetic antagonistic MR1 ligand. Methods Oxazolone colitis was induced in MR1−/− mice (C57BL/6 background), their littermate wild-type controls, and C57BL/6 mice orally administered an antagonistic MR1 ligand, isobutyl 6-formyl pterin (i6-FP). Cytokine production of splenocytes and colonic lamina propria lymphocytes from mice receiving i6-FP was analyzed. Intestinal permeability was assessed in MR1−/− and i6-FP-treated mice and their controls. The effect of i6-FP on cytokine production by MAIT cells from patients with UC was assessed. Results MR1 deficiency or i6-FP treatment reduced the severity of oxazolone colitis. i6-FP treatment reduced cytokine production in MAIT cells from mice and patients with UC. Although MR1 deficiency increased the intestinal permeability, i6-FP administration did not affect gut integrity in mice. Conclusions These results indicate MAIT cells have a pathogenic role in colitis and suppression of MAIT cell activation might reduce the severity of colitis without affecting gut integrity. Thus, MAIT cells are potential therapeutic targets for inflammatory bowel disease including UC. Graphical abstract |
| Databáze: | OpenAIRE |
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