Abstract
BackgroundAlcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear.ResultsIn this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8.ConclusionsOur findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.
Highlights
Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases worldwide
We found there are no significant changes in the frequency of Mucosal-associated invariant T (MAIT) cells in alcoholic cirrhosis patients who had abstained from alcohol over 1 year, compared with patients who had still been excessive drinking (p = 0.076) (Fig. 1E)
In line with previous studies [8], we found that apoptosis may be one of reasons of MAIT cell loss in patients with alcoholic cirrhosis, possibly through activation-induced cell death
Summary
Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases worldwide. Mucosal-associated invariant T (MAIT) cells are innate immune cells that are abundant in the liver [7]. MAIT cells can be activated by riboflavin metabolites derived from microorganism. MAIT cells can be activated by IL-12, IL-18, IL-15 and IL-23. MAIT cells can be considered both non-specific immune and acquired immune cells. MAIT cells are associated with the progression of HBV infection [13]. Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. The changes of MAIT cell in ALD remains unclear
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