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

Nat Immunol. 2020 Nov;21(11):1421-1429. doi: 10.1038/s41590-020-0776-4. Epub 2020 Sep 14.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anxiety / etiology*
  • Anxiety / metabolism*
  • Anxiety / psychology
  • Behavior, Animal
  • Cell Proliferation
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Disease Models, Animal
  • Dura Mater
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Meninges / immunology
  • Meninges / metabolism
  • Mice
  • Mice, Knockout
  • Neurons / immunology*
  • Neurons / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Transcriptome

Substances

  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta