Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice

IntroductionDiabetic ocular complications include sight-threatening consequences and decreased corneal sensitivity, characterized by decreased tear production, corneal sensitivity and delayed corneal epithelial wound healing. The pathogenesis of diabetic corneal disorders remains largely unknown. Gr...

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Main Authors: Limin Qin, Qian Li, Liqiang Wang, Yifei Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1253188/full
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author Limin Qin
Limin Qin
Limin Qin
Qian Li
Qian Li
Qian Li
Liqiang Wang
Yifei Huang
author_facet Limin Qin
Limin Qin
Limin Qin
Qian Li
Qian Li
Qian Li
Liqiang Wang
Yifei Huang
author_sort Limin Qin
collection DOAJ
description IntroductionDiabetic ocular complications include sight-threatening consequences and decreased corneal sensitivity, characterized by decreased tear production, corneal sensitivity and delayed corneal epithelial wound healing. The pathogenesis of diabetic corneal disorders remains largely unknown. Growing evidence implies the participation of immune cells in the development of diabetic corneal diseases. Nonetheless, the immunological changes that result in diabetic corneal problems are largely unknown.MethodsMass cytometry by time of flight (CyTOF) was used to investigate immune cell cluster alterations associated with diabetic corneal disorders. CyTOF test was performed on corneal cells at a single level from 21-week-old diabetic (db/db) and non-diabetic (db/m) mice. A panel of 41 immune-related markers monitored different immune cell types in diabetic corneas. To investigate the proportion of each immune cell subpopulation, an unsupervised clustering method was employed, and T-distributed stochastic neighbor embedding was used to visualize the distinctions between different immune cell subsets.ResultsThrough CyTOF test, we identified 10 immune cell subsets in the corneal tissues. In a novel way, we discovered significant immune alterations in diabetic corneas, including pronounced alterations in T cells and myeloid cell subgroups in diabetic corneas linked to potential biomarkers, including CD103, CCR2, SiglecF, Ly6G, and CD172a. Comprehensive immunological profiling indicated remarkable changes in the immune microenvironment in diabetic corneas, characterized by a notable decrease in CD103+CD8+ tissue-resident memory T (TRM) cells and Tregs, as well as a dramatic increase of γδT cells and subsets of CD11b+Ly6G+ myeloid-derived suppressor cells (MDSCs).ConclusionCyTOF analysis revealed significant alterations in the immune microenvironment during the development of diabetic corneal complications. This study mapped the immune microenvironment landscape of type 2 diabetic corneas, providing a fundamental understanding of immune-driven diabetic corneal disorders.
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spelling doaj.art-de936c6d9ee849baab42515e1be34c4d2023-09-05T06:54:04ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-09-011410.3389/fendo.2023.12531881253188Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic miceLimin Qin0Limin Qin1Limin Qin2Qian Li3Qian Li4Qian Li5Liqiang Wang6Yifei Huang7Department of Ophthalmology, The Third Medical Center, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaDepartment of Ophthalmology, The First Medical Center, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaDepartment of Ophthalmology, Medical School of Chinese People’s Liberation Army (PLA), Beijing, ChinaDepartment of Ophthalmology, The Third Medical Center, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaDepartment of Ophthalmology, The First Medical Center, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaDepartment of Ophthalmology, Medical School of Chinese People’s Liberation Army (PLA), Beijing, ChinaDepartment of Ophthalmology, The Third Medical Center, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaDepartment of Ophthalmology, The Third Medical Center, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaIntroductionDiabetic ocular complications include sight-threatening consequences and decreased corneal sensitivity, characterized by decreased tear production, corneal sensitivity and delayed corneal epithelial wound healing. The pathogenesis of diabetic corneal disorders remains largely unknown. Growing evidence implies the participation of immune cells in the development of diabetic corneal diseases. Nonetheless, the immunological changes that result in diabetic corneal problems are largely unknown.MethodsMass cytometry by time of flight (CyTOF) was used to investigate immune cell cluster alterations associated with diabetic corneal disorders. CyTOF test was performed on corneal cells at a single level from 21-week-old diabetic (db/db) and non-diabetic (db/m) mice. A panel of 41 immune-related markers monitored different immune cell types in diabetic corneas. To investigate the proportion of each immune cell subpopulation, an unsupervised clustering method was employed, and T-distributed stochastic neighbor embedding was used to visualize the distinctions between different immune cell subsets.ResultsThrough CyTOF test, we identified 10 immune cell subsets in the corneal tissues. In a novel way, we discovered significant immune alterations in diabetic corneas, including pronounced alterations in T cells and myeloid cell subgroups in diabetic corneas linked to potential biomarkers, including CD103, CCR2, SiglecF, Ly6G, and CD172a. Comprehensive immunological profiling indicated remarkable changes in the immune microenvironment in diabetic corneas, characterized by a notable decrease in CD103+CD8+ tissue-resident memory T (TRM) cells and Tregs, as well as a dramatic increase of γδT cells and subsets of CD11b+Ly6G+ myeloid-derived suppressor cells (MDSCs).ConclusionCyTOF analysis revealed significant alterations in the immune microenvironment during the development of diabetic corneal complications. This study mapped the immune microenvironment landscape of type 2 diabetic corneas, providing a fundamental understanding of immune-driven diabetic corneal disorders.https://www.frontiersin.org/articles/10.3389/fendo.2023.1253188/fulltissue-resident memory Tmyeloid-derived suppressor cellsγδ T cellsimmune microenvironmenthyperglycemia
spellingShingle Limin Qin
Limin Qin
Limin Qin
Qian Li
Qian Li
Qian Li
Liqiang Wang
Yifei Huang
Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
Frontiers in Endocrinology
tissue-resident memory T
myeloid-derived suppressor cells
γδ T cells
immune microenvironment
hyperglycemia
title Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
title_full Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
title_fullStr Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
title_full_unstemmed Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
title_short Mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
title_sort mass cytometry reveals the corneal immune cell changes at single cell level in diabetic mice
topic tissue-resident memory T
myeloid-derived suppressor cells
γδ T cells
immune microenvironment
hyperglycemia
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1253188/full
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