TY - JOUR
T1 - Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons
AU - Alves de Lima, Kalil
AU - Rustenhoven, Justin
AU - Da Mesquita, Sandro
AU - Wall, Morgan
AU - Salvador, Andrea Francesca
AU - Smirnov, Igor
AU - Martelossi Cebinelli, Guilherme
AU - Mamuladze, Tornike
AU - Baker, Wendy
AU - Papadopoulos, Zach
AU - Lopes, Maria Beatriz
AU - Cao, William Sam
AU - Xie, Xinmin Simon
AU - Herz, Jasmin
AU - Kipnis, Jonathan
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85090924829&partnerID=8YFLogxK
U2 - 10.1038/s41590-020-0776-4
DO - 10.1038/s41590-020-0776-4
M3 - Article
C2 - 32929273
AN - SCOPUS:85090924829
SN - 1529-2908
VL - 21
SP - 1421
EP - 1429
JO - Nature immunology
JF - Nature immunology
IS - 11
ER -