美国弗吉尼亚大学Jonathan Kipnis和Kalil Alves de Lima课题组的一项最新研究提出，脑膜γδT细胞通过调控神经元中白细胞介素（IL）-17a信号调节焦虑行为。该研究于2020年9月14日发表于国际学术期刊《自然-免疫学》。

通过对脑膜γδ17T细胞的细胞和分子表征，研究人员确定了体稳态条件下与IL-17a相关最近的中枢神经系统来源。在出生后不久脑膜γδT细胞就表达高水平的趋化因子受体CXCR6和脑膜起始细胞。在生理条件下这些细胞产生的IL-17a与小鼠焦虑行为相关，并且部分取决于T细胞受体参与和共生的信号。IL-17a受体在稳态皮质谷氨酸能神经元中表达，其遗传缺失降低了小鼠的焦虑行为。

这项发现表明，脑膜γδ17T细胞产生IL-17a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。

据介绍，LI-17a在脊椎动物免疫系统进化过程中一直高度保守，并在感染和自身免疫领域得到了广泛研究。研究表明，在自闭症实验模型中IL-17a可促进个体的行为变化和蠕虫的聚集行为。

附：英文原文

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

Author: Kalil Alves de Lima, Justin Rustenhoven, Sandro Da Mesquita, Morgan Wall, Andrea Francesca Salvador, Igor Smirnov, Guilherme Martelossi Cebinelli, Tornike Mamuladze, Wendy Baker, Zach Papadopoulos, Maria Beatriz Lopes, William Sam Cao, Xinmin Simon Xie, Jasmin Herz, Jonathan Kipnis

Issue&Volume: 2020-09-14

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.

DOI: 10.1038/s41590-020-0776-4

Source: https://www.nature.com/articles/s41590-020-0776-4