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 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.

Regulatory T cells and cardiovascular diseases

“…[94] Th17/Treg imbalance can exacerbate autoimmune myocarditis. [95] Dilated cardiomyopathy (DCM) Immunopathogenic pathways may play a role in the development of DCM, which is characterized by ventricular enlargement and compromised myocardial contractility. [96] In individuals with DCM, the number and function of Tregs are compromised, and Tregs produce a high amount of IFN-g. [97] Decreased abundance of latentassociated peptide + Tregs, impaired TGF-b secretion, and defective contact-dependent mechanisms were observed in DCM.…”