Induction, function and regulation of IL-17-producing T cells

Eur J Immunol. 2008 Oct;38(10):2636-49. doi: 10.1002/eji.200838535.

Abstract

Recent reports have provided convincing evidence that IL-17-producing T cells play a key role in the pathogenesis of organ-specific autoimmune diseases, a function previously attributed exclusively to IFN-gamma-secreting Th1 cells. Furthermore, it appears that IL-17-producing T cells can also function with Th1 cells to mediate protective immunity to pathogens. Although much of the focus has been on IL-17-secreting CD4+ T cells, termed Th17 cells, CD8+ T cells, gammadelta T cells and NKT cells are also capable of secreting IL-17. The differentiation of Th17 cells from naïve T cells appears to involve signals from TGF-beta, IL-6, IL-21, IL-1beta and IL-23. Furthermore, IL-1alpha or IL-1beta in synergy with IL-23 can promote IL-17 secretion from memory T cells. The induction or function of Th17 cells is regulated by cytokines secreted by the other major subtypes of T cells, including IFN-gamma, IL-4, IL-10 and at high concentrations, TGF-beta. The main function of IL-17-secreting T cells is to mediate inflammation, by stimulating production of inflammatory cytokines, such as TNF-alpha, IL-1beta and IL-6, and inflammatory chemokines that promote the recruitment of neutrophils and macrophages.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • Cytokines / biosynthesis
  • Cytokines / immunology*
  • Humans
  • Immune System Diseases / immunology
  • Infections / immunology
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism*
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Interleukin-17
  • Intracellular Signaling Peptides and Proteins
  • Toll-Like Receptors
  • Transcription Factors