Zhu Z.-F.,Huazhong University of Science and Technology |
Zhu Z.-F.,Key Laboratory of Biological Targeted Therapy of the Ministry of Education |
Tang T.-T.,Huazhong University of Science and Technology |
Tang T.-T.,Key Laboratory of Biological Targeted Therapy of the Ministry of Education |
And 28 more authors.
Journal of Leukocyte Biology | Year: 2015
There has been increasing evidence that chronic immune activation plays critical roles in the pathogenesis of DCM. CD4+ LAP+ Tregs are a newly identified T cell subset with suppressive function on the immune response. This study was designed to investigate whether the circulating frequency and function of CD4+LAP+ Tregs would be impaired in patients with DCM. The results demonstrated that DCM patients had a significantly lower frequency of circulating CD4+LAP+ Tregs compared with control donors. CD4+LAP+ Tregs from DCM patients showed compromised function to suppress proliferation of CD4+ LAP2CD25int/low T cells and proliferation and IgG production of B cells. Moreover, B cell proliferation and IgG subset production could be directly suppressed by CD4+ LAP+ Tregs. TGF-b and contact-dependent mechanisms were involved in CD4+LAP+ Treg-mediated suppression. Correlation analysis suggested that CD4+LAP+ Treg frequency was positively correlated with LVEF and negatively correlated with serum IgG3 and NT-proBNP concentration in patients with DCM. Our results are the first to demonstrate that the frequencies of CD4+LAP+ Tregs in patients with DCM are reduced and that their suppressive function is compromised. Defective CD4+ LAP+ Tregs may be an underlying mechanism of immune activation in DCM patients. © Society for Leukocyte Biology. Source
Zhou S.-F.,Huazhong University of Science and Technology |
Zhou S.-F.,Key Laboratory of Biological Targeted Therapy of the Ministry of Education |
Yuan J.,Huazhong University of Science and Technology |
Yuan J.,Key Laboratory of Biological Targeted Therapy of the Ministry of Education |
And 29 more authors.
Journal of Molecular Medicine | Year: 2014
Inflammatory responses play an important role in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We previously demonstrated that interleukin (IL)-17A plays a pathogenic role in myocardial ischemia/reperfusion injury and viral myocarditis. However, the role of IL-17A in post-MI remodeling and the related mechanisms have not been fully elucidated. Acute MI was induced by permanent ligation of the left anterior descending coronary artery in C57BL/6 mice. Repletion of IL-17A significantly aggravated both early- and late-phase ventricular remodeling, as demonstrated by increased infarct size, deteriorated cardiac function, increased myocardial fibrosis, and cardiomyocyte apoptosis. By contrast, genetic IL-17A deficiency had the opposite effect. Additional studies in vitro indicated that IL-17A induces neonatal cardiomyocyte (from C57BL/6 mice) apoptosis through the activation of p38, p53 phosphorylation, and Bax redistribution. These data demonstrate that IL-17A induces cardiomyocyte apoptosis through the p38 mitogen-activated protein kinase (MAPK)-p53-Bax signaling pathway and promotes both early- and late-phase post-MI ventricular remodeling. IL-17A might be an important target in preventing heart failure after MI. © 2014, Springer-Verlag Berlin Heidelberg. Source