期刊
NATURE NEUROSCIENCE
卷 24, 期 6, 页码 818-830出版社
NATURE PORTFOLIO
DOI: 10.1038/s41593-021-00837-1
关键词
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资金
- 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]
Xu et al. developed a new animal model of maternal immune activation using a parasite mimetic, showing that immune and behavioral abnormalities in adult offspring can be reversed by adoptive transfer of regulatory T cells. Notably, pathogen-activated maternal T-reg cells show greater rescue efficacy than those from control donors.
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.
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