Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals

Immunity. 2009 Aug 21;31(2):321-30. doi: 10.1016/j.immuni.2009.06.020. Epub 2009 Aug 13.

Abstract

Gammadelta T cells are an innate source of interleukin-17 (IL-17), preceding the development of the adaptive T helper 17 (Th17) cell response. Here we show that IL-17-producing T cell receptor gammadelta (TCRgammadelta) T cells share characteristic features with Th17 cells, such as expression of chemokine receptor 6 (CCR6), retinoid orphan receptor (RORgammat), aryl hydrocarbon receptor (AhR), and IL-23 receptor. AhR expression in gammadelta T cells was essential for the production of IL-22 but not for optimal IL-17 production. In contrast to Th17 cells, CCR6(+)IL-17-producing gammadelta T cells, but not other gammadelta T cells, express Toll-like receptors TLR1 and TLR2, as well as dectin-1, but not TLR4 and could directly interact with certain pathogens. This process was amplified by IL-23 and resulted in expansion, increased IL-17 production, and recruitment of neutrophils. Thus, innate receptor expression linked with IL-17 production characterizes TCRgammadelta T cells as an efficient first line of defense that can orchestrate an inflammatory response to pathogen-derived as well as environmental signals long before Th17 cells have sensed bacterial invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Infections / immunology*
  • Basic Helix-Loop-Helix Transcription Factors
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-23 / genetics
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukins / immunology
  • Interleukins / metabolism
  • Lectins, C-Type
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / microbiology
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / immunology
  • Receptors, Aryl Hydrocarbon / metabolism
  • Receptors, CCR6 / immunology
  • Receptors, CCR6 / metabolism
  • Receptors, Retinoic Acid / immunology
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / immunology
  • Receptors, Thyroid Hormone / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / microbiology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Helper-Inducer / microbiology
  • Toll-Like Receptor 1 / immunology
  • Toll-Like Receptor 1 / metabolism
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism

Substances

  • Ahr protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • CCR6 protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Aryl Hydrocarbon
  • Receptors, CCR6
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • dectin 1
  • interleukin-22