Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy

Shimiao Bu; Jiang-Yue Ling; Xiaojun Wu; Liting Zhang; Xiangyu Shi; Lang Huang; Zheng Zhao; Ying Yang; Zongqin Xiang; Yong U Liu; Yufeng Liu; Yuehong Zhang

doi:10.3389/fendo.2024.1509445

Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy

Front Endocrinol (Lausanne). 2025 Jan 8:15:1509445. doi: 10.3389/fendo.2024.1509445. eCollection 2024.

Authors

Shimiao Bu^#^{1

2}, Jiang-Yue Ling^#^{1

2}, Xiaojun Wu^#^{1

2}, Liting Zhang^{1

2}, Xiangyu Shi¹, Lang Huang², Zheng Zhao³, Ying Yang³, Zongqin Xiang², Yong U Liu^{2

4}, Yufeng Liu², Yuehong Zhang^{1

2}

Affiliations

¹ Department of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
² 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.
³ Department of Neurology, The First Affiliated Hospital, School of Medicine, Jinan University, Guangzhou, China.
⁴ Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, University of South China, Hengyang, China.

^# Contributed equally.

Abstract

Objective: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: MERTK; PBMC (peripheral blood mononuclear cells); diabetes mellitus; non-proliferative diabetic retinopathy; retinopathy.

MeSH terms

Adult
Aged
Case-Control Studies
Diabetes Mellitus, Type 2* / blood
Diabetes Mellitus, Type 2* / metabolism
Diabetic Retinopathy* / blood
Diabetic Retinopathy* / genetics
Diabetic Retinopathy* / metabolism
Diabetic Retinopathy* / pathology
Down-Regulation*
Female
Humans
Leukocytes, Mononuclear / metabolism
Male
Middle Aged
T-Lymphocytes* / metabolism
c-Mer Tyrosine Kinase* / genetics
c-Mer Tyrosine Kinase* / metabolism

Substances

c-Mer Tyrosine Kinase
MERTK protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (Grant No. 8217060280 to YL and No. 82071188 to YUL), Natural Science Foundation of Guangdong Province (Grant No. 2023A1515010376 to YZ), and Natural Science Foundation of Guangzhou Municipality, China (Grant No. 2023A03J0479 to YZ).