Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons

Kalil Alves de Lima, Justin Rustenhoven, Sandro Da Mesquita, Morgan Wall, Andrea Francesca Salvador, Igor Smirnov, Guilherme Martelossi Cebinelli, Tornike Mamuladze, Wendy Baker, Zach Papadopoulos, Maria Beatriz Lopes, William Sam Cao, Xinmin Simon Xie, Jasmin Herz, Jonathan Kipnis

Research output: Contribution to journalArticlepeer-review

210 Scopus citations


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.

Original languageEnglish
Pages (from-to)1421-1429
Number of pages9
JournalNature immunology
Issue number11
StatePublished - Nov 1 2020


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