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

被引：282

作者：

Alves de Lima, Kalil ^{[1
,2
,3
]}

Rustenhoven, Justin ^{[1
,2
,3
]}

Da Mesquita, Sandro ^{[1
,2
]}

Wall, Morgan ^{[1
,2
]}

Salvador, Andrea Francesca ^{[1
,2
,3
]}

Smirnov, Igor ^{[1
,2
,3
]}

Martelossi Cebinelli, Guilherme ^{[1
,2
,4
]}

Mamuladze, Tornike ^{[1
,2
,3
]}

Baker, Wendy ^{[1
,2
]}

Papadopoulos, Zach ^{[1
,2
,3
]}

Lopes, Maria Beatriz ^{[5
]}

Cao, William Sam ^{[6
]}

Xie, Xinmin Simon ^{[6
]}

Herz, Jasmin ^{[1
,2
,3
]}

Kipnis, Jonathan ^{[1
,2
,3
]}

机构：

[1] Univ Virginia, Ctr Brain Immunol & Glia BIG, Charlottesville, VA 22903 USA

[2] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA

[3] Washington Univ, Div Immunobiol, Dept Pathol & Immunol, St Louis, MO 63110 USA

[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Res Inflammatory Dis CRID, Sao Paulo, Brazil

[5] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA

[6] AfaSci Res Labs, Redwood City, CA USA

来源：

NATURE IMMUNOLOGY | 2020年 / 21卷 / 11期

基金：

美国国家卫生研究院;

关键词：

HOMEOSTASIS; IMMUNITY; PACKAGE; GENE;

D O I：

10.1038/s41590-020-0776-4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

IL-17a is an evolutionarily conserved cytokine with behavior-modulating roles in the central nervous system. Kipnis and colleagues characterize a population of meningeal gamma delta 17 T cells that use IL-17a to elicit anxiety-like behavior through cortical glutamatergic neurons. 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 gamma delta 17 T cells, we defined the nearest central nervous system-associated source of IL-17a under homeostasis. Meningeal gamma delta 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 gamma delta 17 T cells represents an evolutionary bridge between this conserved anti-pathogen molecule and survival behavioral traits in vertebrates.

引用

页码：1421 / +

页数：31

共 39 条

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