Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX, 77555-1062, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Sci Rep. 2024 Nov 18;14(1):28417. doi: 10.1038/s41598-024-79795-0.
Fetal microchimerism, the presence of fetal cells in maternal tissues, has garnered interest for its potential role in maternal physiology. In this study, we aimed to explore the impact of fetal microchimeric cells on maternal lung health following term and preterm delivery, particularly in the context of infection-induced preterm birth and subsequent allergic challenges. We characterized the immune cells in maternal lungs using a transgenic mouse model (mT+ Ve, Td Tomato) and high dimensional mass cytometry (CyTOF) techniques. We evaluated their influence on lung function and inflammation. Our findings revealed distinct differences in the immune cell composition of maternal lungs between term and preterm deliveries. Mice delivered preterm significantly increased in fetal-specific cells, such as activated macrophages and Tbet + Ve memory B-cells, compared to term-delivered mice. Conversely, term deliveries showed elevated levels of CD4 cells. Furthermore, preterm-delivered dams demonstrated heightened airway hyperresponsiveness, pro-inflammatory cytokine expression, cellular infiltration, and lung mucous production compared to term-delivered dams. Co-culture experiments demonstrated that microchimeric cells from preterm births stimulated the production of inflammatory cytokines IL-6 and TNF-α in lung epithelial cells. These findings shed light on the complex immune dynamics postpartum and their role in lung complications after preterm birth. Understanding these mechanisms could provide insights for targeted interventions to improve maternal lung health in at-risk populations.
胎儿微嵌合体,即胎儿细胞存在于母体组织中,因其在母体生理学中的潜在作用而受到关注。在这项研究中,我们旨在探讨胎儿微嵌合细胞对足月和早产分娩后母体肺健康的影响,特别是在感染诱导的早产和随后的过敏挑战背景下。我们使用转基因小鼠模型(mT+ Ve,Td Tomato)和高维质谱流式细胞术(CyTOF)技术来研究母体肺中的免疫细胞。我们评估了它们对肺功能和炎症的影响。我们的研究结果揭示了足月和早产分娩后母体肺中免疫细胞组成的明显差异。与足月分娩的小鼠相比,早产分娩的小鼠中胎儿特异性细胞(如活化的巨噬细胞和 Tbet+ Ve 记忆 B 细胞)显著增加。相反,足月分娩的小鼠中 CD4 细胞水平升高。此外,与足月分娩的母鼠相比,早产分娩的母鼠表现出更高的气道高反应性、促炎细胞因子表达、细胞浸润和肺粘液产生。共培养实验表明,来自早产的微嵌合细胞刺激肺上皮细胞产生炎症细胞因子 IL-6 和 TNF-α。这些发现揭示了产后复杂的免疫动态及其在早产后肺并发症中的作用。了解这些机制可能为针对高危人群改善母体肺健康的靶向干预提供思路。