Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.
Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.
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DOI：
10.1038/s41590-020-0776-4
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发表时间：
2020-11
影响因子：
30.5
通讯作者：
Kipnis J
中科院分区：
文献类型：
--
作者：
Alves de Lima K;Rustenhoven J;Da Mesquita S;Wall M;Salvador AF;Smirnov I;Martelossi Cebinelli G;Mamuladze T;Baker W;Papadopoulos Z;Lopes MB;Cao WS;Xie XS;Herz J;Kipnis J
白细胞介素-17 a（IL-17 a）在脊椎动物免疫系统的进化过程中高度保守，并在感染和自身免疫的背景下被广泛研究。研究表明，IL-17 a促进自闭症实验模型的行为变化和蠕虫的聚集行为。在这里，通过脑膜γδ17 T细胞的细胞和分子表征，我们定义了在稳态下最接近的中枢神经系统相关的IL-17 α来源。脑膜γδ T细胞表达高水平的趋化因子受体CXCR 6，并在出生后不久接种脑膜。这些细胞的IL-17 a的生理释放与小鼠的焦虑样行为相关，并且部分依赖于T细胞受体结合和神经细胞来源的信号。IL-17 a受体在稳态下在小鼠皮层神经元中表达，其基因缺失降低小鼠的焦虑样行为。我们的研究结果表明，脑膜γδ17 T细胞产生的IL-17 a代表了这种保守的抗病原体分子与脊椎动物生存行为特征之间的进化桥梁。
Interleukin-17a (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.
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影响因子：
64.8
作者：
Filiano AJ;Xu Y;Tustison NJ;Marsh RL;Baker W;Smirnov I;Overall CC;Gadani SP;Turner SD;Weng Z;Peerzade SN;Chen H;Lee KS;Scott MM;Beenhakker MP;Litvak V;Kipnis J
通讯作者：
Kipnis J
影响因子：
8.8
作者：
Homdli, Cornelia N. Stacher;Wong, Eleanor;Gregg, Christopher
通讯作者：
Gregg, Christopher
脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
影响因子：
5.4
作者：
Koenecke, Christian;Chennupati, Vijaykumar;Prinz, Immo
通讯作者：
Prinz, Immo
影响因子：
--
作者：
Nowicka, Malgorzata;Krieg, Carsten;Robinson, Mark D
通讯作者：
Robinson, Mark D