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Soluble Fgl2 restricts autoimmune hepatitis progression via suppressing Tc17 and conventional CD8+ T cell function
Author(s) -
Ai Guo,
Yan Weiming,
Yu Haijing,
Xiao Fang,
Xi Dong,
Ma Ke,
Huang Jiaquan,
Luo Xiaoping,
Wan Xiaoyang,
Ning Qin
Publication year - 2018
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3023
Subject(s) - autoimmune hepatitis , immunology , medicine , cd8 , immune system , inflammation , t cell , fibrosis , hepatitis
Background Autoimmune hepatitis (AIH) is an inflammatory disease caused by an aberrant immune response to hepatic self‐antigens in which regulatory T cells (Tregs) are critical for maintaining immunosupression. The soluble form of fibrinogen‐like protein 2 (sFGL2), a novel effector molecule of Treg, is rarely investigated in AIH. In the present study, we dissected the role of sFGL2 in autoimmune hepatitis and its potential mechanism underlying AIH progression. Methods Plasma and intrahepatic sFGL2 levels, as well as Treg cells, were measured in both AIH patients and experimental autoimmune hepatitis (EAH) mice. Th1, Th2, Th17 and Treg‐related cytokines were measured in the liver of EAH mice. Treg expression of sFgl2 and its effect on CD8+ T cell activity in EAH were assessed. The clinical relevance of sFGL2 in AIH‐associated inflammation and fibrosis was evaluated. Results Th17 responses is predominant in robust AIH patients and EAH mice. In AIH patients and EAH mice, the frequency of plasma Tregs was reduced, whereas intrahepatic Tregs were increased significantly. The plasma sFGL2 level was significantly higher at active phases compared to those during remission and was correlated with AIH progression. Enhanced sFGL2 expression was found in Tregs and inhibited conventional CD8+ T cells and Tc17 cell in EAH mice ex vivo . Conclusions The Th17 response dominates autoimmune hepatitis progression. The increase in intrahepatic and plasma sFGL2 by Tregs may restrict AIH progression by inhibiting conventional CD8+ T cells and Tc17 cell function. The high correlation between sFGL2 and disease severity may predict AIH outcome.