Yujue Zhang1, Yuanyuan Fan2, Wei He3, Yi Han4, Huarui Bao5, Renjun Yang1, Bingbing Wang1, Derun Kong6,7, Hua Wang8,9. 1. Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. 2. Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China. 3. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China. 4. Department of Gastroenterology, Fuyang Hospital of Anhui Medical University, Fuyang, 236000, Anhui, P.R. China. 5. Department of Emergency, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. 6. Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. kongderun168@163.com. 7. Department of Gastroenterology, Fuyang Hospital of Anhui Medical University, Fuyang, 236000, Anhui, P.R. China. kongderun168@163.com. 8. Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China. wanghua@ahmu.edu.cn. 9. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, Anhui, China. wanghua@ahmu.edu.cn.
Abstract
BACKGROUND: Alcohol-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. RESULTS: In 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. CONCLUSIONS: Our 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.
BACKGROUND:Alcohol-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. RESULTS: In 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. CONCLUSIONS: Our 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.
Authors: Helmut K Seitz; Ramon Bataller; Helena Cortez-Pinto; Bin Gao; Antoni Gual; Carolin Lackner; Philippe Mathurin; Sebastian Mueller; Gyongyi Szabo; Hidekazu Tsukamoto Journal: Nat Rev Dis Primers Date: 2018-08-16 Impact factor: 52.329