The mechanisms involved in the immune activation observed during the progression of human chronic heart failure and dilated cardiomyopathy have not been fully elucidated . However, a number of recent studies suggest that, besides genetic susceptibility and infections, chronic immune-mediated inflammation after acute myocarditis may lead to dilated cardiomyopathy. This report investigates the role of the leukocyte activation antigen CD69 in the modulation of the inflammatory response in a mouse model of autoimmune myocarditis. Our data demonstrate that CD69, through the regulation of Th17 effector responses, limits myocardial inflammation and subsequent heart failure. It is very feasible that a similar phenomenon occurs in humans with myocarditis and subsequent dilated cardiomyopathy . These findings reveal the involvement of a novel molecular actor in the immunopathogenesis of myocarditis, which could be a potential therapeutic target.