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A deleterious role for Th9/IL-9 in hepatic fibrogenesis

Sci Rep. 2016 Jan 5:6:18694. doi: 10.1038/srep18694.

Abstract

T helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-β1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen, and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-β1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / pharmacology
  • Case-Control Studies
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / metabolism
  • Humans
  • Immunophenotyping
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / blood
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Interleukin-9 / antagonists & inhibitors
  • Interleukin-9 / blood
  • Interleukin-9 / genetics
  • Interleukin-9 / metabolism*
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Lymphocyte Count
  • Male
  • Mice
  • Middle Aged
  • RNA, Messenger / genetics
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / pathology
  • T-Lymphocyte Subsets*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Cytokines
  • Interleukin-17
  • Interleukin-9
  • RNA, Messenger