Bu Shimiao, Ling Jiang-Yue, Wu Xiaojun, Zhang Liting, Shi Xiangyu, Huang Lang, Zhao Zheng, Yang Ying, Xiang Zongqin, Liu Yong U, Liu Yufeng, Zhang Yuehong
Department of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Laboratory for Neuroimmunology in Health and Diseases, Center for Medical Research on Innovation and Translation, Institute of Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Front Endocrinol (Lausanne). 2025 Jan 8;15:1509445. doi: 10.3389/fendo.2024.1509445. eCollection 2024.
To explore the differential gene expression in peripheral blood immune cells of individuals with type 2 diabetes mellitus (DM), comparing those with and without non-proliferative diabetic retinopathy (NPDR).
From a pool of 126 potential participants, 60 were selected for detailed analysis. This group included 12 healthy donors (HDs), 22 individuals with DM, and 26 with NPDR. We analyzed peripheral blood mononuclear cells (PBMCs) using RNA sequencing and quantitative PCR (qPCR) to pinpoint differentially expressed genes (DEGs). Western blot and flow cytometry were also employed to evaluate the protein expression of specific genes.
In patients with NPDR compared to those with DM alone, MerTK-a gene implicated in inherited retinal dystrophies due to its mutations-was notably downregulated in PBMCs. Through flow cytometry, we assessed the protein levels and cellular distribution of MerTK, finding a predominant expression in monocytes and myeloid-derived suppressor cells (MDSCs), with a marked reduction in CD4+ and CD8+ T cells, as well as in natural killer T (NKT) cells. Patients with DM demonstrated a significant deviation in the PBMCs composition, particularly in B cells, CD4+ T cells, and NK cells, when compared to HDs.
The study indicates that MerTK expression in T cells within PBMCs could act as a viable blood biomarker for NPDR risk in patients with DM. Furthermore, the regulation of T cells by MerTK might represent a critical pathway through which DM evolves into NPDR.
探讨2型糖尿病（DM）患者外周血免疫细胞中的差异基因表达，比较有无非增殖性糖尿病视网膜病变（NPDR）的患者。
从126名潜在参与者中选出60名进行详细分析。该组包括12名健康供者（HD）、22名DM患者和26名NPDR患者。我们使用RNA测序和定量PCR（qPCR）分析外周血单个核细胞（PBMC），以确定差异表达基因（DEG）。还采用蛋白质印迹法和流式细胞术评估特定基因的蛋白质表达。
与仅患有DM的患者相比，NPDR患者中，因突变而与遗传性视网膜营养不良有关的MerTK-a基因在PBMC中显著下调。通过流式细胞术，我们评估了MerTK的蛋白质水平和细胞分布，发现其在单核细胞和髓系来源的抑制性细胞（MDSC）中主要表达，在CD4+和CD8+ T细胞以及自然杀伤T（NKT）细胞中明显减少。与HD相比，DM患者的PBMC组成存在显著差异，尤其是在B细胞、CD4+ T细胞和NK细胞中。
该研究表明，PBMC中T细胞内的MerTK表达可能作为DM患者NPDR风险的一种可行血液生物标志物。此外，MerTK对T细胞的调节可能代表DM演变为NPDR的关键途径。
