Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals.
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.
Martin
Bruno
B
Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Hirota
Keiji
K
Cua
Daniel J
DJ
Stockinger
Brigitta
B
Veldhoen
Marc
M
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051194:Toll-Like Receptor 1 / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22; D000099181:Dectin-1
D051792:Basic Helix-Loop-Helix Proteins; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018336:Receptors, Aryl Hydrocarbon; D054399:Receptors, CCR6; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D000097043:Interleukin-22; D000099181:Dectin-1; C484722:Ahr protein, mouse; C498126:CCR6 protein, mouse; C539901:Rorc protein, mouse