The pathogenicity of Th17 cells in autoimmune diseases

Semin Immunopathol. 2019 May;41(3):283-297. doi: 10.1007/s00281-019-00733-8. Epub 2019 Mar 19.

Abstract

IL-17-producing T helper (Th17) cells have been implicated in the pathogenesis of many inflammatory and autoimmune diseases. Targeting the effector cytokines IL-17 and GM-CSF secreted by autoimmune Th17 cells has been shown to be effective for the treatment of the diseases. Understanding a molecular basis of Th17 differentiation and effector functions is therefore critical for the regulation of the pathogenicity of tissue Th17 cells in chronic inflammation. Here, we discuss the roles of proinflammatory cytokines and environmental stimuli in the control of Th17 differentiation and chronic tissue inflammation by pathogenic Th17 cells in humans and in mouse models of autoimmune diseases. We also highlight recent advances in the regulation of pathogenic Th17 cells by gut microbiota and immunometabolism in autoimmune arthritis.

Keywords: Autoimmune arthritis; EAE; GM-CSF; IL-17; Rheumatoid arthritis; Th17 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / metabolism
  • Autoimmunity*
  • Cell Differentiation / immunology
  • Cytokines / metabolism
  • Disease Susceptibility*
  • Environmental Exposure
  • Gastrointestinal Microbiome
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-17 / biosynthesis
  • Lymphocyte Activation / immunology
  • Phenotype
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism

Substances

  • Cytokines
  • IL17A protein, human
  • Inflammation Mediators
  • Interleukin-17