The rebalancing of the immune system at the maternal-fetal interface ameliorates autism-like behavior in adult offspring
Chunxiang Shen,
Xinyi Zhu,
Hao Chang,
Chen Li,
Min Hou,
Lin Chen,
Lu Chen,
Zikai Zhou,
Minjun Ji,
Zhipeng Xu
Affiliations
Chunxiang Shen
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Xinyi Zhu
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Hao Chang
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Chen Li
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Min Hou
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 211166, P.R. China
Lin Chen
Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 211166, P.R. China
Lu Chen
Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 211166, P.R. China
Zikai Zhou
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, Guangdong 528400, P.R. China; Corresponding author
Minjun Ji
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 211166, P.R. China; NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China; Corresponding author
Zhipeng Xu
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu 211166, P.R. China; NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China; Corresponding author
Summary: Maternal immune activation (MIA) is critical for imparting neuropathology and altered behaviors in offspring; however, maternal-fetal immune cell populations have not been thoroughly investigated in MIA-induced autism spectrum disorders (ASDs). Here, we report the single-cell transcriptional landscape of placental cells in both PBS- and poly(I:C)-induced MIA dams. We observed a decrease in regulatory T (Treg) cells but an increase in the M1 macrophage population at the maternal-fetal interface in MIA dams. Based on the Treg-targeting approach, we investigate an immunoregulatory protein, the helminth-derived heat shock protein 90α (Sjp90α), that induces maternal Treg cells and subsequently rescues the autism-like behaviors in adult offspring. Furthermore, in vivo depletion of maternal macrophages attenuates placental inflammatory reaction and reverses behavioral abnormalities in adult offspring. Notably, Sjp90α induces CD4+ T cell differentiation via scavenger receptor A (SR-A) on the macrophage in vitro. Our findings suggest a maternal Treg-targeted approach to alleviate MIA-induced autism-like behavior in adult offspring.
