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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Infections / immunology*
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Basic Helix-Loop-Helix Transcription Factors
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Interleukin-17 / immunology*
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Interleukin-17 / metabolism
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Interleukin-22
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Interleukin-23 / genetics
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Interleukin-23 / immunology
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Interleukin-23 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Interleukins / immunology
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Interleukins / metabolism
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Lectins, C-Type
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Nerve Tissue Proteins / immunology
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Nerve Tissue Proteins / metabolism
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Neutrophils / immunology
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Neutrophils / metabolism
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Neutrophils / microbiology
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Antigen, T-Cell, gamma-delta / immunology*
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / immunology
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Receptors, Aryl Hydrocarbon / metabolism
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Receptors, CCR6 / immunology
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Receptors, CCR6 / metabolism
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Receptors, Retinoic Acid / immunology
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Receptors, Retinoic Acid / metabolism
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Receptors, Thyroid Hormone / immunology
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Receptors, Thyroid Hormone / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / microbiology
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Helper-Inducer / microbiology
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Toll-Like Receptor 1 / immunology
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Toll-Like Receptor 1 / metabolism
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / immunology
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Toll-Like Receptor 2 / metabolism
Substances
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Ahr protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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CCR6 protein, mouse
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Interleukin-17
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Interleukin-23
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Interleukin-6
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Interleukins
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Lectins, C-Type
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Membrane Proteins
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Nerve Tissue Proteins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Aryl Hydrocarbon
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Receptors, CCR6
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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Toll-Like Receptor 1
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Toll-Like Receptor 2
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dectin 1