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Nat Immunol ; 21(11): 1421-1429, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32929273

RESUMO

Interleukin (IL)-17a has been highly conserved during evolution of the vertebrate immune system and widely studied in contexts of infection and autoimmunity. Studies suggest that IL-17a promotes behavioral changes in experimental models of autism and aggregation behavior in worms. Here, through a cellular and molecular characterization of meningeal γδ17 T cells, we defined the nearest central nervous system-associated source of IL-17a under homeostasis. Meningeal γδ T cells express high levels of the chemokine receptor CXCR6 and seed meninges shortly after birth. Physiological release of IL-17a by these cells was correlated with anxiety-like behavior in mice and was partially dependent on T cell receptor engagement and commensal-derived signals. IL-17a receptor was expressed in cortical glutamatergic neurons under steady state and its genetic deletion decreased anxiety-like behavior in mice. Our findings suggest that IL-17a production by meningeal γδ17 T cells represents an evolutionary bridge between this conserved anti-pathogen molecule and survival behavioral traits in vertebrates.


Assuntos
Ansiedade/etiologia , Ansiedade/metabolismo , Interleucina-17/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Ansiedade/psicologia , Comportamento Animal , Proliferação de Células , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Dura-Máter , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interleucina-17/genética , Meninges/imunologia , Meninges/metabolismo , Camundongos , Camundongos Knockout , Receptores de Antígenos de Linfócitos T gama-delta/genética , Transdução de Sinais , Transcriptoma
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