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 - Funding Information:
We thank S. Smith for editing the manuscript, J. Sokolowski for help with the collection of human samples and M. Beenhakker for help with interpreting the electrophysiology studies. We thank all members of the Kipnis laboratory and members of the Center for Brain Immunology and Glia (BIG) for valuable comments during multiple discussions of this work. We also thank the UVA Flow Cytometry Core for help with cell sorting, the Genome Analysis and Technology Core for help with library preparation and sequencing, and J. Graham from the Virginia Commonwealth University School of Nursing for performing the Meso Scale Discovery assay. This work was supported by grants from the National Institutes of Health (MH108156, AT010416 and AG034113) to J.K.
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 -