Liu Xiuxing, Zhu Lei, Huang Zhaohao, Li Zhaohuai, Duan Runping, Li He, Xie Lihui, Chen Xiaozhen, Ding Wen, Chen Binyao, Gao Yuehan, Su Juan, Wang Xianggui, Su Wenru
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-Sen University, Guangzhou 510060, China.
Eye Center of Xiangya Hospital, Central South University, Changsha 410078, China.
Fundam Res. 2022 Jun 30;5(1):391-406. doi: 10.1016/j.fmre.2022.06.011. eCollection 2025 Jan.
Extensive immune adaptations occur during pregnancy to ensure successful delivery. However, these changes can increase the risk of disease in the mother. Here, we conducted single-cell RNA sequencing on peripheral blood mononuclear cells from pregnant women at different stages of pregnancy to elucidate the dynamic transcriptional changes in the maternal immune system. Gradual reduced cytotoxicity phenotype in highly variable cytotoxic T and natural killer cell types were observed during pregnancy. Reduced T- and B-cell response-related MHC-II and CD40 signaling as well as enhanced protolerance inducible costimulator and activin signaling may underlie the pregnancy-related weakening of adaptive immunity. Conversely, pro-inflammatory genes and pathways were upregulated in monocytes, possibly to compensate for the reduced T-cell response. Moreover, the transition from adaptive immune reduction to activation in late pregnancy in dendritic cells and CD4 T cells was also detected. Notably, we proposed a novel view of the pro-aging effect of pregnancy from the perspective of immunity, and this effect may be restored postpartum. This work expands our knowledge of pregnancy immunity and may provide insights into the altered disease risks during pregnancy.
孕期会发生广泛的免疫适应以确保分娩顺利。然而,这些变化会增加母亲患病的风险。在此,我们对处于不同孕期阶段的孕妇外周血单个核细胞进行了单细胞RNA测序,以阐明母体免疫系统的动态转录变化。在孕期观察到高变细胞毒性T细胞和自然杀伤细胞类型的细胞毒性表型逐渐降低。与T细胞和B细胞反应相关的MHC-II和CD40信号传导减少,以及诱导共刺激分子和激活素信号传导增强导致的免疫耐受增强,可能是孕期适应性免疫减弱的基础。相反,单核细胞中的促炎基因和信号通路上调,可能是为了弥补T细胞反应的降低。此外,还检测到树突状细胞和CD4 T细胞在妊娠晚期从适应性免疫降低向激活的转变。值得注意的是,我们从免疫角度提出了孕期促衰老作用的新观点,且这种作用可能在产后恢复。这项工作扩展了我们对孕期免疫的认识,并可能为孕期疾病风险改变提供见解。