Characterization of progesterone-induced dendritic cells in metabolic and immunologic reprogramming

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.