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

ObjectiveTo 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).MethodsFrom a pool of 126 potential participants, 60 were selected for detailed anal...

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Main Authors: 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1509445/full
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author Shimiao Bu
Shimiao Bu
Jiang-Yue Ling
Jiang-Yue Ling
Xiaojun Wu
Xiaojun Wu
Liting Zhang
Liting Zhang
Xiangyu Shi
Lang Huang
Zheng Zhao
Ying Yang
Zongqin Xiang
Yong U. Liu
Yong U. Liu
Yufeng Liu
Yuehong Zhang
Yuehong Zhang
author_facet Shimiao Bu
Shimiao Bu
Jiang-Yue Ling
Jiang-Yue Ling
Xiaojun Wu
Xiaojun Wu
Liting Zhang
Liting Zhang
Xiangyu Shi
Lang Huang
Zheng Zhao
Ying Yang
Zongqin Xiang
Yong U. Liu
Yong U. Liu
Yufeng Liu
Yuehong Zhang
Yuehong Zhang
author_sort Shimiao Bu
collection DOAJ
description ObjectiveTo 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).MethodsFrom 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.ResultsIn 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. ConclusionsThe 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.
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spelling doaj-art-822cb99c6ac14c2794899708ffac53052025-01-08T05:10:32ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011510.3389/fendo.2024.15094451509445Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathyShimiao Bu0Shimiao Bu1Jiang-Yue Ling2Jiang-Yue Ling3Xiaojun Wu4Xiaojun Wu5Liting Zhang6Liting Zhang7Xiangyu Shi8Lang Huang9Zheng Zhao10Ying Yang11Zongqin Xiang12Yong U. Liu13Yong U. Liu14Yufeng Liu15Yuehong Zhang16Yuehong Zhang17Department of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaLaboratory 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, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaLaboratory 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, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaLaboratory 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, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaLaboratory 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, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaLaboratory 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, ChinaDepartment of Neurology, The First Affiliated Hospital, School of Medicine, Jinan University, Guangzhou, ChinaDepartment of Neurology, The First Affiliated Hospital, School of Medicine, Jinan University, Guangzhou, ChinaLaboratory 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, ChinaLaboratory 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, ChinaDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, University of South China, Hengyang, ChinaLaboratory 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, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaLaboratory 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, ChinaObjectiveTo 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).MethodsFrom 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.ResultsIn 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. ConclusionsThe 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.https://www.frontiersin.org/articles/10.3389/fendo.2024.1509445/fulldiabetes mellitusretinopathynon-proliferative diabetic retinopathyPBMC (peripheral blood mononuclear cells)MERTK
spellingShingle Shimiao Bu
Shimiao Bu
Jiang-Yue Ling
Jiang-Yue Ling
Xiaojun Wu
Xiaojun Wu
Liting Zhang
Liting Zhang
Xiangyu Shi
Lang Huang
Zheng Zhao
Ying Yang
Zongqin Xiang
Yong U. Liu
Yong U. Liu
Yufeng Liu
Yuehong Zhang
Yuehong Zhang
Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy
Frontiers in Endocrinology
diabetes mellitus
retinopathy
non-proliferative diabetic retinopathy
PBMC (peripheral blood mononuclear cells)
MERTK
title Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy
title_full Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy
title_fullStr Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy
title_full_unstemmed Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy
title_short Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy
title_sort downregulation of mertk in circulating t cells of patients with non proliferative diabetic retinopathy
topic diabetes mellitus
retinopathy
non-proliferative diabetic retinopathy
PBMC (peripheral blood mononuclear cells)
MERTK
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1509445/full
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