Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis

Abstract Objective Autoimmune myocarditis is caused by both innate and adaptive immune responses. Many studies have found that myeloid‐derived suppressor cells (MDSCs) suppress T‐cell responses and reduce immune tolerance, while MDSCs may serve as a key player in inflammatory responses and pathogene...

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Main Authors: Xin Xiong, Mengjia Yu, Dinghang Wang, Yange Wang, Longxian Cheng
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.872
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author Xin Xiong
Mengjia Yu
Dinghang Wang
Yange Wang
Longxian Cheng
author_facet Xin Xiong
Mengjia Yu
Dinghang Wang
Yange Wang
Longxian Cheng
author_sort Xin Xiong
collection DOAJ
description Abstract Objective Autoimmune myocarditis is caused by both innate and adaptive immune responses. Many studies have found that myeloid‐derived suppressor cells (MDSCs) suppress T‐cell responses and reduce immune tolerance, while MDSCs may serve as a key player in inflammatory responses and pathogenesis in variety of autoimmune diseases. However, research into the role of MDSCs in experimental autoimmune myocarditis (EAM) remains lacking. Methods and Results We discovered that the expansion of MDSCs in EAM was closely related to the severity of myocardial inflammation. At an early stage of EAM, both adoptive transfer (AT) and selective depletion of MDSCs could inhibit the expression of IL‐17 in CD4+ cells and downregulate the Th17/Treg ratio, alleviating excessive inflammation of EAM myocarditis. In another experiment, in addition, MDSCs transferred after selective depletion could increase IL‐17 and Foxp3 expressions in CD4+ cells, as well as the Th17/Treg ratio, contributing to the aggravation of myocardial inflammation. MDSCs promoted the Th17 cell induction under Th17‐polarizing conditions in vitro but suppressed Treg expansion. Conclusion These findings suggest that MDSCs play a plastic role in sustaining mild inflammation in EAM by shifting Th17/Treg balance.
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series Immunity, Inflammation and Disease
spelling doaj-art-cb9a2670c6e84b9d909173589df475212025-08-20T01:53:08ZengWileyImmunity, Inflammation and Disease2050-45272023-06-01116n/an/a10.1002/iid3.872Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditisXin Xiong0Mengjia Yu1Dinghang Wang2Yange Wang3Longxian Cheng4Department of Pediatrics, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Emergency, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Cardiology the First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaLaboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract Objective Autoimmune myocarditis is caused by both innate and adaptive immune responses. Many studies have found that myeloid‐derived suppressor cells (MDSCs) suppress T‐cell responses and reduce immune tolerance, while MDSCs may serve as a key player in inflammatory responses and pathogenesis in variety of autoimmune diseases. However, research into the role of MDSCs in experimental autoimmune myocarditis (EAM) remains lacking. Methods and Results We discovered that the expansion of MDSCs in EAM was closely related to the severity of myocardial inflammation. At an early stage of EAM, both adoptive transfer (AT) and selective depletion of MDSCs could inhibit the expression of IL‐17 in CD4+ cells and downregulate the Th17/Treg ratio, alleviating excessive inflammation of EAM myocarditis. In another experiment, in addition, MDSCs transferred after selective depletion could increase IL‐17 and Foxp3 expressions in CD4+ cells, as well as the Th17/Treg ratio, contributing to the aggravation of myocardial inflammation. MDSCs promoted the Th17 cell induction under Th17‐polarizing conditions in vitro but suppressed Treg expansion. Conclusion These findings suggest that MDSCs play a plastic role in sustaining mild inflammation in EAM by shifting Th17/Treg balance.https://doi.org/10.1002/iid3.872autoimmune myocarditis in experimentbalanceinflammationmyeloid‐derived suppressor cellsTh17 cellsTreg
spellingShingle Xin Xiong
Mengjia Yu
Dinghang Wang
Yange Wang
Longxian Cheng
Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
Immunity, Inflammation and Disease
autoimmune myocarditis in experiment
balance
inflammation
myeloid‐derived suppressor cells
Th17 cells
Treg
title Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
title_full Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
title_fullStr Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
title_full_unstemmed Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
title_short Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
title_sort th17 treg balance is regulated by myeloid derived suppressor cells in experimental autoimmune myocarditis
topic autoimmune myocarditis in experiment
balance
inflammation
myeloid‐derived suppressor cells
Th17 cells
Treg
url https://doi.org/10.1002/iid3.872
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AT dinghangwang th17tregbalanceisregulatedbymyeloidderivedsuppressorcellsinexperimentalautoimmunemyocarditis
AT yangewang th17tregbalanceisregulatedbymyeloidderivedsuppressorcellsinexperimentalautoimmunemyocarditis
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