Associate Professor of Medicine Tokyo Medical and Dental University Tokyo, Tokyo, Japan
Abstract Text: Background &
Aim: We have previously reported that the activation status of the circulating mucosal-associated invariant T (MAIT) cells in patients with ulcerative colitis (UC) is associated with the severity, and these cells infiltrate the inflamed lesion. These observations imply that MAIT cells are involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of MAIT cells in the setting of IBD has not been unveiled. Therefore, we investigated the role of MAIT cells in an animal model of UC. Methods &
Results: We utilized major histocompatibility complex-related molecule 1 deficient mice (MR1-/-), which lack MAIT cells, and isobutyl 6-formyl pterin (i6-FP), which is a synthetic antagonistic MR1 ligand. Wild-type (WT) C57BL/6 mice administered an oral i6-FP or MR1-/- were sensitized with oxazolone to induce colitis. MR1 deficiency or i6-FP treatment resulted in reduced severity of colitis. Splenocytes and colonic lamina propria lymphocytes were isolated from mice receiving i6-FP. Treatment with i6-FP resulted in reduced MAIT cell production of pro-inflammatory cytokines such as IFN-g and TNF. Reduced cytokine production by MAIT cells were also observed in peripheral blood mononuclear cells from the patients with UC when incubated with i6-FP. MR1-/- and i6-FP-treated WT were orally administered FITC-dextran. Although MR1 deficiency resulted in increased intestinal permeability, i6-FP administration did not affect gut integrity in mice.
Conclusion: These results indicate that MAIT cells have a pathogenic role in colitis and suppressing activation of these cells may reduce the severity. Thus, MAIT cells are potential therapeutic targets for IBD.
