Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4(+) T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4(+)CD25(+)GARP(+) regulatory T (Treg) cells in DCM. Forty-five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon- (IFN-), interleukin (IL-17)], and an obvious decrease in Treg number, transforming growth factor-(1) (TGF-(1)) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4(+)CD25(+)GARP(+) Treg cells was impaired in DCM patients upon T-cell receptor stimulation detected using CFSE dye. Lower level of TGF-(1) and higher levels of IFN- and IL-17 detected using ELISA were found in supernatants of the cultured CD4(+)CD25(+)GARP(+) Treg cells in DCM patients compared with controls. Together, our results indicate that CD4(+)CD25(+)GARP(+) Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients.

Background Excessive immune‐mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling. Interleukin‐37 (IL‐37) emerges as an inhibitor of both innate and adaptive immunity. However, the exact role of IL‐37 and IL‐37 plus troponin I (TnI)–treated dendritic cells (DCs) in ventricular remodeling after myocardial infarction (MI) remains elusive. Methods and Results MI was induced by permanent ligation of the left anterior descending artery. Our results showed that treatment with recombinant human IL‐37 significantly ameliorated ventricular remodeling after MI, as demonstrated by decreased infarct size, better cardiac function, lower mortality, restricted inflammatory responses, decreased myocardial fibrosis, and inhibited cardiomyocyte apoptosis. In vitro, we examined the phenotype of IL‐37 plus TnI–conditioned DCs of male C57BL/6 mice and their capacity to influence the number of regulatory T cells. Our results revealed that IL‐37 plus TnI–conditioned DCs obtained the characteristics of tolerogenic DCs (tDCs) and expanded the number of regulatory T cells when co‐cultured with splenic CD4+ T cells. Interestingly, we also found that adoptive transfer of these antigen‐loaded tDCs markedly increased the number of regulatory T cells in the spleen, attenuated the infiltration of inflammatory cells in the infarct hearts, decreased myocardial fibrosis, and improved cardiac function. Conclusions Our results reveal a beneficial role of IL‐37 or tDCs treated with IL‐37 plus TnI in post‐MI remodeling that is possibly mediated by reestablishing a tolerogenic immune response, indicating that IL‐37 or adoptive transfer of IL‐37 plus TnI–treated tDCs may be a novel therapeutic strategy for ventricular remodeling after MI.