小柯机器人

上海交通大学医学院周子凯、南京医科大学季旻珺等研究人员合作发现，病原体激活的母体T_reg细胞能够挽救母体免疫激活诱导的成年小鼠后代行为异常 。2021年4月15日，《自然—神经科学》杂志在线发表了这项成果。

研究人员使用了来自弓形虫的速殖子抗原（一种感染约20亿人的寄生虫）来诱导小鼠母体免疫激活（MIA）。成年雄性后代表现出与自闭症相关的行为和异常的大脑微结构，以及周围星形胶质细胞的促炎性T细胞免疫谱和脑星形胶质细胞中白介素6的上调。研究人员表明调节性T（T_reg）细胞的过继转移大大扭转了这些MIA诱导的表型。

值得注意的是，病原体激活的母体T_reg细胞比对照供体具有更高的挽救功效。单细胞RNA测序鉴定并鉴定了一组独特的病原体激活的T_reg细胞，这些细胞构成了病原体激活的母体T_reg群体的32.6％。这项研究建立了一种新的临床前模仿寄生虫的MIA模型，并提出了过继性T_reg细胞转移在与免疫改变相关神经精神疾病中的治疗潜力。

据悉，脂多糖或多肌苷酸：聚胞苷酸注射液引起的MIA可以诱导成年小鼠后代的行为异常。

附：英文原文

Title: Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells

Author: Zhipeng Xu, Xiaoyun Zhang, Hao Chang, Yue Kong, Yangyue Ni, Ran Liu, Xiaolin Zhang, Yang Hu, Zhi Yang, Min Hou, Rui Mao, Wen-Tao Liu, Yasong Du, Shunying Yu, Zhen Wang, Minjun Ji, Zikai Zhou

Issue&Volume: 2021-04-15

Abstract: Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii, a parasite that infects approximately two billion people, to induce MIA in mice. The adult male offspring showed autism-relevant behaviors and abnormal brain microstructure, along with a pro-inflammatory T-cell immune profile in the periphery and upregulation of interleukin-6 in brain astrocytes. We show that adoptive transfer of regulatory T (Treg) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal Treg cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated Treg cells that constitute 32.6% of the pathogen-activated maternal Treg population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive Treg cell transfer in neuropsychiatric disorders associated with immune alterations. Xu et al. developed and characterized a new animal model of maternal immune activation based on a parasite mimetic. They show that immune and behavioral abnormalities in adult offspring are reversed by adoptive transfer of regulatory T cells.

DOI: 10.1038/s41593-021-00837-1

Source: https://www.nature.com/articles/s41593-021-00837-1

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex