MRC National Institute for Medical Research, London
Science for Health
Interleukin-17 producing γδ T cells - first off the mark in infection
14 August 2009
The cytokine interleukin-17 (IL-17) plays an important role in orchestrating innate immune function. IL-17 promotes granulopoiesis and neutrophil accumulation in peripheral tissues for pathogen clearance and for host defence against pathogens such as klebsiella pneumoniae or candida albicans. It can also protect mucosal barrier functions due to stimulation of tight junction formation and mucin secretion. The Th17 T helper cell subset is a major source of IL-17 in vivo. Th17 cells differentiate from naïve CD4+ T cells in the presence of interleukin-6 and transforming growth factor-β and have been extensively studied in connection with the development of autoimmune diseases. Gamma-delta ( γδ) T cells, a type of innate T cells that respond more rapidly to bacterial infections than the adaptive Th17 cell, are another source of IL-17. Although γδ T cell-derived IL-17 is one of the earliest sources of this cytokine following infection, there is little information regarding the phenotypic and functional characteristics of IL-17 producing γδ T cells.
Studies in Gitta Stockinger’s lab, in NIMR's Division of Molecular Immunology, have shown that IL-17 producing γδ T cells represent a subset of γδ T cells with similar characteristics to Th17 cells, such as the expression of receptors s uch as the hydrocarbon receptor (AhR), which makes such cells responsive to environmental stimuli. Furthermore, IL-17 producing γδ T cells express pattern recognition receptors that allow them to directly respond to certain pathogens and orchestrate the inflammatory response to such infections. Thus, IL-17 producing γδ T cells represent a central innate protective response to bacterial infection. Furthermore, their function can be enhanced and modulated by the presence of AhR ligands. Additional modulation of their function by environmental signals from endogenous or exogenous sources through the AhR is likely to have implications for the outcome of bacterial infections.
Our results suggest that IL-17 producing TCR γδ T cells are a specialized subset that can not only directly interact with pathogens, but also respond to AhR mediated environmental signals which shape their functional capacity. This puts them in the position of a first line defence team that can orchestrate an inflammatory response leading to recruitment of neutrophils long before Th17 have sensed any bacterial invasion.
Gitta Stockinger
Original Article
The research findings are published in full in:
Bruno Martin, Keiji Hirota, Daniel J Cua, Brigitta Stockinger and Marc Veldhoen (2009)
Interleukin-17 producing γδ T cells selectively expand in response to pathogen products and environmental signals
Immunity, epub ahead of print. Publisher abstract
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