| Literature DB >> 33859437 |
Zhipeng Xu1, Xiaoyun Zhang2,3,4, Hao Chang1, Yue Kong2, Yangyue Ni1, Ran Liu1, Xiaolin Zhang2, Yang Hu2, Zhi Yang2, Min Hou1, Rui Mao2, Wen-Tao Liu1, Yasong Du2, Shunying Yu2, Zhen Wang3, Minjun Ji5,6, Zikai Zhou7,8,9,10.
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.Entities:
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Year: 2021 PMID： 33859437 DOI： 10.1038/s41593-021-00837-1
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884