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

doi:10.1038/s41593-021-00837-1

	Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T-reg cells
	Xu, Zhipeng 1; Zhang, Xiaoyun 2,3,4; Chang, Hao 1; Kong, Yue 2; Ni, Yangyue 1; Liu, Ran 1; Zhang, Xiaolin 2; Hu, Yang 2; Yang, Zhi 2; Hou, Min 1
刊名	NATURE NEUROSCIENCE
	2021-04-15
页码	33
ISSN号	1097-6256
DOI	10.1038/s41593-021-00837-1
通讯作者	Ji, Minjun(jiminjun@njmu.edu.cn) ; Zhou, Zikai(zhouzikai@simm.ac.cn)
英文摘要	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 (T-reg) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T-reg cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T-reg cells that constitute 32.6% of the pathogen-activated maternal T-reg population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T-reg 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.
资助项目	National Natural Science Foundation of China[81971022] ; Program of Shanghai Academic Research Leader[19XD1423300] ; Natural Science Foundation of Jiangsu Province[BK20171049] ; Science and Technology Commission of Shanghai Municipality[201409002600] ; Foundation of Jiangsu Province Key Laboratory of Modern Pathogen Biology[JX218GSP20171003] ; Shanghai Key Laboratory of Psychotic Disorders Open Grant[19-K01] ; Shanghai Mental Health Center-Clinical Research Center[CRC2019ZD01] ; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support[20191835]
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000640476600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295214]
专题	中国科学院上海药物研究所
通讯作者	Ji, Minjun; Zhou, Zikai
作者单位	1.Nanjing Med Univ, Dept Pathogen Biol, State Key Lab Reprod Med, Jiangsu Prov Key Lab Modern Pathogen Biol, Nanjing, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Sch Med, Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery & Dev, Zhongshan, Peoples R China 5.Jiangsu Prov Engn Res Ctr Antibody Drug, Nanjing, Peoples R China 6.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China
推荐引用方式 GB/T 7714	Xu, Zhipeng,Zhang, Xiaoyun,Chang, Hao,et al. Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T-reg cells[J]. NATURE NEUROSCIENCE,2021:33.
APA	Xu, Zhipeng.,Zhang, Xiaoyun.,Chang, Hao.,Kong, Yue.,Ni, Yangyue.,...&Zhou, Zikai.(2021).Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T-reg cells.NATURE NEUROSCIENCE,33.
MLA	Xu, Zhipeng,et al."Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T-reg cells".NATURE NEUROSCIENCE (2021):33.