Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus

Abstract

Background

Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls.

Methods

Clinical parameters and postpartum complications were reviewed in all participants. Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 ⁺ T, CD8 ⁺ T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines.

Results

Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 ⁺ T and CD8 ⁺ T cells than the control group. Interestingly, senescent CD4 ⁺ T cells tended to increase and CD8 ⁺ T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 ⁺) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM.

Conclusion

This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Graphical Abstract