Soluble Fgl2 restricts autoimmune hepatitis progression via suppressing Tc17 and conventional CD8+ T cell function

J Gene Med. 2018 Jul;20(7-8):e3023. doi: 10.1002/jgm.3023. Epub 2018 Jun 19.


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.

Keywords: Tregs; animal model; autoimmune hepatitis; cell immunology; hepatology; inflammation; soluble FGL2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / metabolism*
  • Gene Expression
  • Hepatitis, Autoimmune / diagnosis
  • Hepatitis, Autoimmune / genetics
  • Hepatitis, Autoimmune / immunology*
  • Hepatitis, Autoimmune / metabolism*
  • Humans
  • Immunomodulation*
  • Liver Function Tests
  • Lymphocyte Count
  • Male
  • Mice
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism


  • Cytokines
  • FGL2 protein, human
  • Fibrinogen