1. Meningeal γδ T Cells Regulate Anxiety-Like Behavior via IL-17a Signaling in Neurons
- Author
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Kalil Alves de Lima, Jasmin Herz, Jonathan Kipnis, Igor Smirnov, William Sam Cao, Sandro Da Mesquita, Tornike Mamuladze, Wendy Baker, Xinmin Xie, Morgan Wall, Justin Rustenhoven, Maria Beatriz Lopes, Zach Papadopoulos, Guilherme Cesar Martelossi Cebinelli, and Andrea Francesca Salvador
- Subjects
medicine.medical_treatment ,Central nervous system ,Population ,Anxiety ,Biology ,Mice ,Glutamatergic ,Chemokine receptor ,Meninges ,T-Lymphocyte Subsets ,medicine ,Animals ,Receptor ,education ,Biological Psychiatry ,Cell Proliferation ,Cerebral Cortex ,Mice, Knockout ,Neurons ,education.field_of_study ,Behavior, Animal ,Gene Expression Profiling ,Interleukin-17 ,T-cell receptor ,Interleukin ,Receptors, Antigen, T-Cell, gamma-delta ,Cell biology ,Disease Models, Animal ,medicine.anatomical_structure ,Cytokine ,Gene Expression Regulation ,Dura Mater ,Transcriptome ,Signal Transduction - Abstract
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. IL-17a is an evolutionarily conserved cytokine with behavior-modulating roles in the central nervous system. Kipnis and colleagues characterize a population of meningeal γδ17 T cells that use IL-17a to elicit anxiety-like behavior through cortical glutamatergic neurons.
- Published
- 2021