State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
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.
Cell Rep. 2024 Oct 22;43(10):114787. doi: 10.1016/j.celrep.2024.114787. Epub 2024 Sep 24.
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.
母体免疫激活 (MIA) 对于在后代中引起神经病理学和行为改变至关重要；然而，在母体免疫激活诱导的自闭症谱系障碍 (ASD) 中，母体-胎儿免疫细胞群体尚未得到彻底研究。在这里，我们报告了 PBS 和聚肌苷酸：聚胞苷酸 (poly(I:C)) 诱导的 MIA 母鼠胎盘细胞的单细胞转录组图谱。我们观察到在 MIA 母鼠的母体-胎儿界面处，调节性 T (Treg) 细胞减少，但 M1 巨噬细胞群体增加。基于针对 Treg 的方法，我们研究了一种免疫调节蛋白，即寄生虫来源的热休克蛋白 90α (Sjp90α)，它诱导母体 Treg 细胞，随后挽救成年后代的自闭症样行为。此外，体内耗尽母源巨噬细胞可减轻胎盘炎症反应并逆转成年后代的行为异常。值得注意的是，Sjp90α 通过体外巨噬细胞上的清道夫受体 A (SR-A) 诱导 CD4 T 细胞分化。我们的研究结果表明，针对母体 Treg 的方法可减轻成年后代 MIA 诱导的自闭症样行为。
