CD3bright signals on γδ T cells identify IL‐17A‐producing Vγ6Vδ1+ T cells

Abstract

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 CD3bright γδ T‐cell subset with an effector memory phenotype to rapidly produce IL‐17A, but not interferon‐γ. CD3bright 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 CD3bright 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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 11, 2014
Source ID
10.1038/icb.2014.94

Entities

People

  • A P Uldrich
  • C Paget
  • D A Mogilenko
  • D Dombrowicz
  • D I Godfrey
  • D S Ritchie
  • D Staumont‐sallé
  • F Souza‐fonseca‐guimaraes
  • F Trottein
  • G T Belz
  • G. R. Hill
  • H Duret
  • M Hassane
  • M J Smyth
  • M T Chow
  • N A Gherardin
  • N K Escalante
  • P A Beavis
  • P Neeson
  • T Mallevaey

Organizations

  • Agence Nationale de la Recherche
  • Canadian Institutes of Health Research
  • Cancer Research Institute
  • Fondation de France
  • Institut Pasteur de Lille
  • National Center for Scientific Research
  • National Health and Medical Research Council
  • Peter MacCallum Cancer Centre
  • QIMR Berghofer Medical Research Institute
  • Royal Brisbane and Women's Hospital
  • United States Department of Defense
  • University Lille-II
  • University of Melbourne
  • University of Queensland
  • University of Toronto
  • WEHI

Tags

Fields of Study

  • Medicine

Readers

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  • Immunology
  • Immunology and Pathology