Characterizations of mucosal associated invariant T cells in alcoholic liver disease

Abstract

Abstract The liver is a critical immunological site for chronic alcohol consumption as it filters various antigens activating both innate and adaptive responses. The pathogenesis of alcoholic liver disease (ALD) in human is not clear in terms of the specific role of immune cell population. Mucosal associated invariant T (MAIT) cells are found to be abundant in the mucosal organs, especially within the liver organ in which the cells comprise up to 50 % of T cells. Here, we show that the percentage of circulating MAIT cells is severely reduced in ALD patients (p=0.0028), including patients with steatohepatitis (ASH, n=20), steatohepatitis with cirrhosis (ASHAC, n=15) and cirrhosis (AC, n=12), compared to age-matched healthy donors (HD, n=8). Moreover, compared to non-liver disease group, MAIT cells are depleted among liver infiltrating lymphocytes in ASH (p=0.0276) and ASHAC (p=0.0049) patients, whereas that of AC group is recovered. Although the percentage of MAIT cells is decreased, the cells display increased expression level of activation markers. Pro-inflammatory cytokines such as IL-17A and MIP-1 beta are up-regulated in ASH and ASHAC patients by PMA/Ionomycin stimulation. In addition, Perforin and Granzyme B, which are cytotoxic markers in granule, are significantly increased in both peripheral blood and liver of ASHAC group. Taken together, our results suggest that activated MAIT cell population in the liver may contribute to the pathogenesis of ALD.