Thymic stromal lymphopoietin modulates T cell response to improve cardiac repair post-myocardial infarction

The inflammatory response is associated with cardiac repair and ventricular remodeling after myocardial infarction (MI). The key inflammation regulatory factor thymic stromal lymphopoietin (TSLP) plays a critical role in various diseases. However, its role in cardiac repair after MI remains uncertain. In this study, we elucidated the biological function and mechanism of action of TSLP in cardiac repair and ventricular remodeling following MI. Wild-type and TSLP receptor (TSLPR)-knockout (Crlf2-/-) mice underwent MI induction via ligation of the left descending artery. TSLP expression was upregulated in the infarcted heart, with a peak observed on day 7 post-MI. TSLP expression was enriched in the cardiomyocytes of infarcted hearts, with the highest expression observed in dendritic cells. Crlf2-/- mice exhibited significantly reduced survival and worsened cardiac function, increased interstitial fibrosis and cardiomyocyte cross-sectional area, and reduced CD31+ staining, with no change in the proportion of apoptotic cardiomyocytes within the border zone. Mechanistically, a reduction in regulatory T cells and more innate immune cells and their subsets were observed in the infarcted hearts of Crlf2-/- mice, accompanied by a systemic reduction in T cell activation and proliferation. Simultaneously, RNA sequencing analysis of the infarcted hearts revealed significant downregulation of genes in Crlf2-/- mice. Our findings indicate that TSLP plays a pivotal role in regulating T cell responses, specifically T regulatory cells, thus promoting cardiac repair, which may provide a potential novel therapeutic approach for managing heart failure after MI.