<b>Possible involvement of mucosal-associated invariant T cells in the progression of inflammatory bowel </b><b>diseases </b>

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in anti-bacterial im-munity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals. Lymphocytes were isolated from the blood and colon, and then MAIT cells were analyzed by flow cytometry. The frequency of MAIT cells was significantly lower in the blood of IBD patients compared to healthy donors and significantly higher in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD patients, the frequency of MAIT cells in the blood and colon was correlated with disease activities. In vitro activated MAIT cells from IBD patients secreted significantly more tumor necrosis factor-α and interleukin-17 than those from healthy donors. These findings indicate that MAIT cells are activated in IBD patients, and their accumulation in the inflamed mucosa is correlated with disease activities.Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic, relapsing inflammatory conditions of the gastrointestinal tract. Although host genetic susceptibility and environmental factors have been implicated in causing the disturbed homeostasis of the intestinal immune system that results in IBD, the exact etiology of IBD is still unknown (11,19,20). Genetic variants clearly play a central role in conferring risk for IBD, but a wide range of environmental factors, including smoking, diet drugs, social stress, and microbial factors, are also thought to confer risk for IBD (2). Accumulating evidence has suggested that among those environmental factors, the dynamic balance between commensal flora and host defensive responses within the intestinal mucosa plays a pivotal role in both the initiation and per-

Persistent reduction of mucosal‐associated invariant T cells in primary biliary cholangitis

“…21 We also reported that MAIT cells accumulated in the inflamed colonic mucosa of IBD patients, although MAIT cells were significantly decreased in the blood of those patients. 27 However, the present study revealed that MAIT cells were significantly decreased in the liver of PBC patients in addition to being reduced in the blood. Consistent with our findings, Jeffery et al recently reported a decreased frequency of MAIT cells in explanted liver tissues of end-stage PBC patients.…”

“…In contrast, in patients with multiple sclerosis or RA, MAIT cells accumulate in the inflamed foci of diseases . We also reported that MAIT cells accumulated in the inflamed colonic mucosa of IBD patients, although MAIT cells were significantly decreased in the blood of those patients . However, the present study revealed that MAIT cells were significantly decreased in the liver of PBC patients in addition to being reduced in the blood.…”

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells

“…In the case of PSC, and except for the actual inflammation in the liver that could promote gut leakiness, many patients also have concomitant IBD. Interestingly, loss in circulation and accumulation of MAIT cells in inflamed intestine has previously been reported in IBD patients where level of MAIT cells also correlated with disease activity . Yet, we observed no significant differences regarding the MAIT cell loss in patients with PSC and IBD compared to patients with PSC only.…”

MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

“…Tominaga et al. also similarly found lower circulating MAIT cell frequencies in their cohort of IBD patients . However, they did not observe NKG2D upregulation in either PB or colonic MAIT cells, due perhaps to an already high expression level of NKG2D in the control cohort or tissues.…”

“…Whether MAIT cells express and utilize CD16 is not entirely clear. 48 However, they did not observe NKG2D upregulation in either PB or colonic MAIT cells, due perhaps to an already high expression level of NKG2D in the control cohort or tissues. The potential link between high or heightened expression levels of NKG2D in IBD and cell-mediated cytotoxicity will need to be addressed in the future.…”