Interleukin-37 and dendritic cells treated with interleukin-37 plus troponin I ameliorate cardiac remodeling after myocardial infarction

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. © 2016 the authors.