Gestational diabetes mellitus dysregulates the PD-1/PD-L1 axis at the feto-maternal interface

ABSTRACT The most common pregnancy complication is gestational diabetes mellitus (GDM), which is a glucose tolerance disorder. Obesity and older maternal age, which are associated with low-grade systemic inflammation, are the main risk factors for GDM. To evaluate the complexity and differences in the immune landscape at the fetal-maternal interface, we examined the maternally derived tissue, decidua basalis (DB), from healthy women, women with obesity, and women with GDM using flow cytometry, western blot, and gene expression analysis. Our results showed that the immune cell composition of DB is not altered by obesity; however, in GDM pregnancies, the DB displays a dysregulated PD-1/PD-L1 axis and significantly reduced regulatory T cell (Treg) infiltration, suggesting reduced local immunosuppression. Our study provides a detailed picture of the immune landscape at the fetal-maternal interface in normal, obese, and GDM pregnancies. This will aid our understanding of possible dysfunctional immune mechanisms in GDM.