RESUMO
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-1ß. 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.
Assuntos
Complexo CD3/metabolismo , Interleucina-17/biossíntese , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/imunologia , Sequência de Aminoácidos , Aminoquinolinas/farmacologia , Animais , Complexo CD3/química , Proteínas de Transporte/metabolismo , Células Germinativas/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Imiquimode , Imunidade , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-23 , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fenótipo , Pele/efeitos dos fármacos , Pele/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
Natural killer (NK)T cells are innate lymphocytes that release important amount of immunoregulatory cytokines (IFN-gamma and/or IL-4) shortly after T cell receptor engagement by (glyco)lipid antigens presented by the CD1d molecules. Through this property, NKT cells play pivotal role in many physiopathologic situations. Here, we review the current knowledge of the functions and mechanisms of activation of NKT cells during infection, with a particular emphasis on helminthic infections. Recent findings suggest that, although dispensable for host resistance, NKT cells play part in the development of the acquired immune response and in the control of the pathology during murine schistosomiasis.