γδ T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism

Immunity. 2010 Sep 24;33(3):351-63. doi: 10.1016/j.immuni.2010.08.013. Epub 2010 Sep 9.

Abstract

Mice that lack interleukin-23 (IL-23) are resistant to T cell-mediated autoimmunity. Although IL-23 is a maturation factor for T helper 17 (Th17) cells, a subset of γδ T cells expresses the IL-23 receptor (IL-23R) constitutively. Using IL-23R reporter mice, we showed that γδ T cells were the first cells to respond to IL-23 during experimental autoimmune encephalomyelitis (EAE). Although γδ T cells produced Th17 cell-associated cytokines in response to IL-23, their major function was to prevent the development of regulatory T (Treg) cell responses. IL-23-activated γδ T cells rendered αβ effector T cells refractory to the suppressive activity of Treg cells and also prevented the conversion of conventional T cells into Foxp3(+) Treg cells in vivo. Thus, IL-23, which by itself has no direct effect on Treg cells, is able to disarm Treg cell responses and promote antigen-specific effector T cell responses via activating γδ T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmunity*
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Interleukin-17 / biosynthesis
  • Interleukin-23 / physiology*
  • Interleukins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Antigen, T-Cell, gamma-delta / physiology*
  • Receptors, Interleukin / physiology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin
  • interleukin-23 receptor, mouse
  • interleukin-22