Interleukin-1 and IL-23 Induce Innate IL-17 Production From Gammadelta T Cells, Amplifying Th17 Responses and Autoimmunity

Immunity. 2009 Aug 21;31(2):331-41. doi: 10.1016/j.immuni.2009.08.001. Epub 2009 Aug 13.

Abstract

Th17 cells, CD4(+) T cells that secrete interleukin-17 (IL-17), are pathogenic in autoimmune diseases and their development and expansion is driven by the cytokines IL-6, TGF-beta, IL-21, IL-1, and IL-23. However, there are also innate sources of IL-17. Here, we show that gammadelta T cells express IL-23R and the transcription factor RORgammat and produce IL-17, IL-21, and IL-22 in response to IL-1beta and IL-23, without T cell receptor engagement. IL-17-producing gammadelta T cells were found at high frequency in the brain of mice with experimental autoimmune encephalomyelitis (EAE). gammadelta T cells activated by IL-1beta and IL-23 promoted IL-17 production by CD4(+) T cells and increased susceptibility to EAE, suggesting that gammadelta T cells act in an amplification loop for IL-17 production by Th17 cells. Our findings demonstrate that gammadelta T cells activated by IL-1beta and IL-23 are an important source of innate IL-17 and IL-21 and provide an alternative mechanism whereby IL-1 and IL-23 may mediate autoimmune inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology*
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Interleukin-23 / pharmacology
  • Interleukins / immunology
  • Interleukins / metabolism
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / immunology
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-17 / immunology
  • Receptors, Interleukin-17 / metabolism*
  • Receptors, Retinoic Acid / immunology
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / immunology
  • Receptors, Thyroid Hormone / metabolism
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • CD3 Complex
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Interleukins
  • Lipopolysaccharides
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Receptors, Interleukin-17
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • interleukin-23 receptor, mouse
  • interleukin-21
  • interleukin-22