Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
J Reprod Immunol. 2023 Sep;159:104128. doi: 10.1016/j.jri.2023.104128. Epub 2023 Aug 3.
The role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy has been well established. Dendritic cells (DCs) as a crucial part of the decidual microenvironment, have high plasticity in immunogenicity and tolerogenicity. The regulatory mechanisms of DCs phenotype or function at the maternal-fetal interface, however, have not been fully developed. Studies from the field of immunometabolism have highlighted that the metabolic pathways of DCs are closely associated with their immunity. Our previous study showed that progesterone (P4) up-regulated a series of enzymes involved in DCs mitochondrial oxidative phosphorylation and fatty acid metabolism. In this study, we confirmed that P4 induced significant alternations in DCs metabolic pathways, promoting their glycolysis, mitochondrial function, and the dependency and capacity of fatty acids as mitochondrial fuel. Moreover, P4 also increased the inhibitory molecule ILT4 expression on DCs and down-regulated the CD86, which may coordinate their immune tolerance function in pregnancy. Together, our study helps to understand the role of P4 in DCs metabolic and immunologic reprogramming and may provide novel insights into the hormonal immunometabolism regulation of DCs during normal pregnancy.
母体-胎儿免疫耐受在妊娠的建立和维持中起着重要作用。树突状细胞（DCs）作为子宫微环境的关键组成部分，在免疫原性和耐受性方面具有很高的可塑性。然而，DCs 在母体-胎儿界面的表型或功能的调节机制尚未完全阐明。免疫代谢领域的研究强调，DCs 的代谢途径与其免疫功能密切相关。我们之前的研究表明，孕激素（P4）上调了一系列与 DCs 线粒体氧化磷酸化和脂肪酸代谢相关的酶。在这项研究中，我们证实 P4 诱导了 DCs 代谢途径的显著改变，促进了它们的糖酵解、线粒体功能以及对脂肪酸作为线粒体燃料的依赖性和能力。此外，P4 还增加了 DCs 上抑制分子 ILT4 的表达，并下调了 CD86，这可能协调了它们在妊娠中的免疫耐受功能。总之，我们的研究有助于了解 P4 在 DCs 代谢和免疫重编程中的作用，并可能为正常妊娠期间 DCs 的激素免疫代谢调节提供新的见解。
