Liu Zhaoxiang, Zhang Mingqiang, Shi Xiaohu, Zhao Wenhui, Cao Chenxiang, Jin Lixia, Wang Yanlei, Xiao Jianzhong
Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Endocr Connect. 2023 Aug 3;12(9):e230218. doi: 10.1530/EC-23-0218.
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.
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.
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).
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.
免疫细胞的激活在2型糖尿病的进展中起重要作用。本研究旨在探讨髓系来源的抑制性细胞（MDSCs）和调节性T细胞（Tregs）在2型糖尿病中的潜在作用。
共招募了61例诊断为2型糖尿病的患者。回顾临床特征并采集外周血样本。我们计算了不同细胞的百分比。MDSC亚群的频率指的是CD45阳性细胞中粒系MDSCs（G-MDSCs，CD15+CD33+CD11b+CD14-HLA-DR-/低）的百分比以及淋巴细胞加单核细胞中单核系MDSCs（M-MDSCs，CD14+CD15-CD11b+CD33+HLA-DR-/低）的百分比。
2型糖尿病患者中程序性细胞死亡配体1阳性粒系MDSCs（PD-L1+ G-MDSCs）、程序性细胞死亡配体2阳性单核系MDSCs（PD-L2+ M-MDSCs）、PD-L2+ G-MDSC和程序性细胞死亡蛋白1阳性Tregs（PD-1+Tregs）的频率降低。PD-1+ Tregs的频率与PD-L2+ M-MDSCs呈正相关（r = 0.357，P = 0.009），与糖化血红蛋白（HbA1c）、空腹胰岛素水平和腰围呈负相关（r分别为-0.265，P = 0.042；r = -0.260，P = 0.047；r = -0.373，P = 0.005）。
PD-L2+ M-MDSCs和PD-1+ Tregs的减少可能促进效应T细胞的激活，导致2型糖尿病中的慢性低度炎症。这些发现突出了MDSCs和Tregs对2型糖尿病免疫发病机制的作用，并提示它们作为新治疗方法靶点的潜力。
