Decreased programmed cell death ligand 2-positive monocytic myeloid-derived suppressor cells and programmed cell death protein 1-positive T-regulatory cells in patients with type 2 diabetes: implications for immunopathogenesis

Abstract

Objectives

The activation of immune cells plays a significant role in the progression of type 2 diabetes. This study aimed to investigate the potential role of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) in type 2 diabetes.

Methods

A total of 61 patients diagnosed with type 2 diabetes were recruited. Clinical characteristics were reviewed and peripheral blood samples were collected. We calculated the percentage of different cells. Frequencies of MDSC subsets refered to the percentage of G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DR-/low) in CD45 positive cells and the percentage of M-MDSCs (CD14+CD15-CD11b+CD33+HLA-DR-/low) in lymphocytes plus monocytes.

Results

Frequencies of programmed cell death ligand 1-positive granulocytic MDSCs (PD-L1 ⁺ G-MDSCs), programmed cell death ligand 2-positive monocytic MDSCs (PD-L2 ⁺ M-MDSCs), PD-L2 ⁺ G-MDSC, and programmed cell death protein 1-positive Tregs (PD-1 ⁺Tregs) were decreased in patients with type 2 diabetes. The frequency of PD-1 ⁺ Tregs was positively related to PD-L2 ⁺ M-MDSCs ( r= 0.357, P = 0.009) and negatively related to HbA1c ( r = -0.265, P = 0.042), fasting insulin level ( r = −0.260, P = 0.047), and waist circumference ( r = −0.373, P = 0.005).

Conclusions

Decreased PD-L2 ⁺ M-MDSCs and PD-1 ⁺ Tregs may promote effector T cell activation, leading to chronic low-grade inflammation in type 2 diabetes. These findings highlight the contribution of MDSCs and Tregs to the immunopathogenesis of type 2 diabetes and suggest their potential as targets for new therapeutic approaches.