Unveiling the pathophysiology of gestational diabetes: Studies on local and peripheral immune cells

Abstract

Gestational diabetes mellitus (GDM) has been associated with impaired maternal immune response. Our aim was to review the available literature linking immune cells profile to GDM, in order to comprehend the role that different subpopulations play in the development of this pathology. We searched in PubMed for studies published in the last decade on circulating levels and placenta expression of immune cells on GDM. We identified 18 studies with several differences regarding the study design, clinical characteristics, number of participants, cell subpopulation and type of sample. Most studies assessed only one subpopulation either in peripheral blood or placenta and did not analyse functional properties of the cells. The most frequently evaluated immune cells were T lymphocytes, especially regulatory T (Tregs), and natural killer (NK) cells in the peripheral blood, and placental macrophages. No studies analysing B cells were identified, and only one study each evaluating γδT cells, dendritic cell (DC) and monocytes was found. Although there are controversies, at least one study reported positive association between GDM and CD4+(activated), Tregs, Th17 and γδT cells; neutrophil/lymphocyte; NK cell (cytotoxic); macrophages; and monocytes. The number of studies is still small, so caution should be exercised in interpreting the data, and further research is required to validate these findings and establish the role of adaptive and innate immune cells in GDM pathophysiology.

Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level

“…GDM is associated with an impaired maternal immune response. However, few studies have focused on the immune cell composition in GDM (37). We identified various types of immune cells in our specimens, including T/NK cells (1,628), B cells (247), monocytes (1,126) and macrophages (4,306).…”

Comprehensive analysis of DNA methylation and gene expression profiles in gestational diabetes mellitus

“…It is reported that GDM is associated with impaired maternal immune response. [ 26 ] Moreover, the differentially regulated proteins related to GDM identified by Zhao et al [ 27 ] also implicated in immune response and defense response. In addition, the enrichment analysis of the KEGG pathway showed that these MeDEGs were mainly enriched in “Allograft rejection,” “Graft-versus-host disease,” “Type I diabetes mellitus,” and “Autoimmune thyroid disease pathways.” This indicates that GDM is also involved in the pathway of type I diabetes.…”

Dendrobine attenuates gestational diabetes mellitus in mice by inhibiting Th17 cells

“…Numerous studies have demonstrated that Th17 cells participate in the progression and development of diabetes mellitus, as well as GDM 5‐7 . Some publications have demonstrated that Th17 cells might promote GDM development 12,26‐28 . The percentage of Th17 cells and the ratio of Th17 cells to Tregs are significantly higher in GDM patients than non‐GDM pregnant women, and this trend is remarkably reduced after delivery.…”

“…[5][6][7] Some publications have demonstrated that Th17 cells might promote GDM development. 12,[26][27][28] The percentage of Th17 cells and the ratio of Th17 cells to Tregs are significantly higher in GDM patients than non-GDM pregnant women, and this trend is remarkably reduced after delivery. Nevertheless, patients with GDM still have a higher Th17:Treg ratio than pregnant women without GDM even after delivery.…”