CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells.
Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3(bright) γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3(bright) γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1(+) T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL-1β. Finally, we demonstrated that IL-17-producing CD3(bright) γδ T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing Vγ6/Vδ1(+) T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this γδ T-cell subset in respiratory and skin disorders.
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia [3] INSERM U1019, Centre d'Infection et d'Immunité de Lille, Institut Pasteur de Lille, Lille, France [4] University of Lille 2, Lille, France.
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Paget
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia [3] QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
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Chow
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia [3] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
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Gherardin
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
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Beavis
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
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Uldrich
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
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Duret
1] INSERM U1019, Centre d'Infection et d'Immunité de Lille, Institut Pasteur de Lille, Lille, France [2] University of Lille 2, Lille, France.
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Hassane
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
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Souza-Fonseca-Guimaraes
1] University of Lille 2, Lille, France [2] INSERM U1011, Institut Pasteur de Lille, Lille, France [3] European Genomic Institute of Diabetes, Lille, France.
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Mogilenko
1] University of Lille 2, Lille, France [2] INSERM U1011, Institut Pasteur de Lille, Lille, France [3] European Genomic Institute of Diabetes, Lille, France [4] Department of Dermatology, Claude Huriez Hospital, Lille, France.
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Staumont-Sallé
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
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Escalante
1] QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia [2] Department of Bone Marrow Transplantation, Royal Brisbane Hospital, Herston, Queensland, Australia.
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Hill
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
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Neeson
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
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Ritchie
1] University of Lille 2, Lille, France [2] INSERM U1011, Institut Pasteur de Lille, Lille, France [3] European Genomic Institute of Diabetes, Lille, France.
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Dombrowicz
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
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Mallevaey
1] INSERM U1019, Centre d'Infection et d'Immunité de Lille, Institut Pasteur de Lille, Lille, France [2] University of Lille 2, Lille, France.
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Trottein
Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
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Belz
1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia [2] Australian Research Council Centre of Excellence in Advanced Medical Imaging at University of Melbourne, Parkville, Victoria, Australia.
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Godfrey
1] Peter MacCallum Cancer Centre, Cancer Immunology Program, St Andrews Place, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia [3] QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia [4] School of Medicine, University of Queensland, Herston, Queensland, Australia.
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Smyth
D000595:Amino Acid Sequence; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D005854:Germ Cells / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D000077271:Imiquimod; D007109:Immunity; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23; D008168:Lung / Q000187:drug effects / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000634:Aminoquinolines; D017252:CD3 Complex; D002352:Carrier Proteins; D058847:Inflammasomes; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta; C000589613:T-cell receptor Vgamma6, mouse; D000077271:Imiquimod