Gene Joint Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Physiol Genomics. 2024 Dec 1;56(12):855-868. doi: 10.1152/physiolgenomics.00041.2024.
We aimed to determine the peripheral blood mononuclear cell (PBMC) immune profiles of mid- and late-stage pregnant women to establish a foundation for studying pregnancy-related diseases. Peripheral blood samples were collected from three women each during mid- and late-stage pregnancy, and PBMCs were extracted for single-cell RNA sequencing (scRNA-seq). Peripheral blood samples were also collected for flow cytometry analysis to validate the analytical results. HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells significantly differed in quantitative ratio and gene transcript level between women at mid- and late-stage pregnancy. In late pregnancy, cell-to-cell communication was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," exhibited high expression, a gene that may be involved in the regulation of immune-related gene transcription and translation, and insulin signaling pathway, during pregnancy. Monocytes exhibited significant proinflammatory and metabolic properties in mid- and late-stage pregnancy, respectively. Natural killer (NK) cells were mainly involved in T- and B-cell-mediated signaling pathways, and in T cell differentiation, in mid-pregnancy. Enhanced innate immunity of NK cells was observed. Moreover, NK cells expressed genes associated with diabetes-related pathways in late-stage pregnancy. To conclude, we present detailed changes in the immune response occurring in pregnant women from mid- to late-stage gestation, revealing significant differences in PBMC subtypes and molecular properties. These findings provide insights into the physiopathological mechanisms of chronic hepatitis B infection, systemic lupus erythematosus, and gestational diabetes mellitus underlying systemic immune responses during mid- and late-stage pregnancy. There are significant differences in three subtypes of memory/effector T cells (HOPX+ CD4+ T cells, ZNF683+CD8+ T cells, and KLRB1+CD8+ T cells) between mid- and late pregnancy. In late pregnancy, intercellular interaction was enhanced and effector CD8+ T cells highly expressed infection-related pathways. A rare T cell subtype, "XIST+ T cells," may be involved in the regulation of immune-related gene transcription and translation with a strong female bias.
我们旨在确定中晚期孕妇外周血单个核细胞（PBMC）的免疫特征，为研究与妊娠相关的疾病奠定基础。从中晚期妊娠的每位女性中采集外周血样本，提取 PBMC 进行单细胞 RNA 测序（scRNA-seq）。还采集外周血样本进行流式细胞术分析，以验证分析结果。HOPX+CD4+T 细胞、ZNF683+CD8+T 细胞和 KLRB1+CD8+T 细胞在中晚期妊娠女性中的定量比和基因转录水平上存在显著差异。在晚期妊娠时，细胞间通讯增强，效应 CD8+T 细胞高度表达感染相关途径。一种罕见的 T 细胞亚型“XIST+T 细胞”在妊娠期间表现出高表达，该基因可能参与免疫相关基因转录和翻译以及胰岛素信号通路的调节。中晚期妊娠时，单核细胞分别表现出显著的促炎和代谢特性。自然杀伤（NK）细胞主要参与中孕期的 T 和 B 细胞介导的信号通路以及 T 细胞分化。中孕期 NK 细胞的先天免疫增强。此外，NK 细胞在晚期妊娠时表达与糖尿病相关途径相关的基因。总之，我们展示了从中孕期到晚期妊娠孕妇免疫反应的详细变化，揭示了 PBMC 亚型和分子特性的显著差异。这些发现为慢性乙型肝炎感染、系统性红斑狼疮和妊娠糖尿病的生理病理机制提供了新的认识，这些疾病与中晚期妊娠期间的全身免疫反应有关。在记忆/效应 T 细胞的三种亚型（HOPX+CD4+T 细胞、ZNF683+CD8+T 细胞和 KLRB1+CD8+T 细胞）之间存在显著差异。在晚期妊娠时，细胞间相互作用增强，效应 CD8+T 细胞高度表达感染相关途径。一种罕见的 T 细胞亚型“XIST+T 细胞”可能参与免疫相关基因转录和翻译的调节，具有强烈的女性偏向性。
