Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction.

ABSTRACT: Doxorubicin, the most prescribed chemotherapeutic drug, causes dose-dependent cardiotoxicity and heart failure. However, our understanding of the immune response elicited by doxorubicin is limited. Here we show that an aberrant CD8⁺ T cell immune response following doxorubicin-induced cardiac injury drives adverse remodeling and cardiomyopathy. Doxorubicin treatment in non-tumor-bearing mice increased circulating and cardiac IFNγ⁺CD8⁺ T cells and activated effector CD8⁺ T cells in lymphoid tissues. Moreover, doxorubicin promoted cardiac CD8⁺ T cell infiltration and depletion of CD8⁺ T cells in doxorubicin-treated mice decreased cardiac fibrosis and improved systolic function. Doxorubicin treatment induced ICAM-1 expression b

SUBMITTER: Bayer AL 

PROVIDER: S-EPMC12324073 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature