Institute of Life Science, Swansea University Medical School, Swansea, UK.
Maternity and Child Health, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK.
Clin Exp Immunol. 2022 May 13;208(1):114-128. doi: 10.1093/cei/uxac023.
Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surrounding obesity and the maternal immune system. The objective of this study was to consider if immunological changes in pregnancy are influenced by maternal obesity. Peripheral blood was collected from fasted GDM-negative pregnant women at 26-28 weeks of gestation. Analysis was done using immunoassay, flow cytometry, bioenergetics analysis, and cell culture. The plasma profile was significantly altered with increasing BMI, specifically leptin (r = 0.7635), MCP-1 (r = 0.3024), and IL-6 (r = 0.4985). Circulating leukocyte populations were also affected with changes in the relative abundance of intermediate monocytes (r = -0.2394), CD4:CD8 T-cell ratios (r = 0.2789), and NKT cells (r = -0.2842). Monocytes analysed in more detail revealed elevated CCR2 expression and decreased mitochondrial content with increased BMI. However, LPS-stimulated cytokine production and bioenergetic profile of PBMCs were not affected by maternal BMI. The Th profile skews towards Th17 with increasing BMI; Th2 (r = -0.3202) and Th9 (r = -0.3205) cells were diminished in maternal obesity, and CytoStim™-stimulation exacerbates IL-6 (r = 0.4166), IL-17A (r = 0.2753), IL-17F (r = 0.2973), and IL-22 (r = 0.2257) production with BMI, while decreasing IL-4 (r = -0.2806). Maternal obesity during pregnancy creates an inflammatory microenvironment. Successful pregnancy requires Th2-biased responses yet increasing maternal BMI favours a Th17 response that could be detrimental to pregnancy. Further research should investigate key populations of cells identified here to further understand the immunological challenges that beset pregnant women with obesity.
健康妊娠伴随着各种免疫和代谢适应。肥胖的母亲与流产、子痫前期和妊娠糖尿病（GDM）等不良妊娠结局有关，同时对新生儿也有风险。人们对肥胖和母体免疫系统知之甚少。本研究旨在探讨妊娠期间的免疫变化是否受母体肥胖的影响。在妊娠 26-28 周时，采集禁食的 GDM 阴性孕妇的外周血。使用免疫测定法、流式细胞术、生物能量分析和细胞培养进行分析。随着 BMI 的增加，血浆谱发生了显著变化，特别是瘦素（r = 0.7635）、MCP-1（r = 0.3024）和 IL-6（r = 0.4985）。循环白细胞群也受到影响，中间单核细胞的相对丰度发生变化（r = -0.2394）、CD4:CD8 T 细胞比值（r = 0.2789）和 NKT 细胞（r = -0.2842）。进一步分析单核细胞显示，随着 BMI 的增加，CCR2 表达增加，线粒体含量减少。然而，LPS 刺激的 PBMCs 细胞因子产生和生物能量谱不受母体 BMI 的影响。随着 BMI 的增加，Th 谱向 Th17 倾斜；Th2（r = -0.3202）和 Th9（r = -0.3205）细胞在母体肥胖中减少，而 CytoStim™刺激会加剧 IL-6（r = 0.4166）、IL-17A（r = 0.2753）、IL-17F（r = 0.2973）和 IL-22（r = 0.2257）的产生与 BMI 呈正相关，同时减少 IL-4（r = -0.2806）。妊娠期间的母体肥胖会产生炎症微环境。成功的妊娠需要 Th2 偏向的反应，但增加的母体 BMI 有利于 Th17 反应，这可能对妊娠不利。进一步的研究应该调查这里确定的关键细胞群体，以进一步了解困扰肥胖孕妇的免疫挑战。
