Thymic Bmi-1 hampers γδT17 generation and its derived RORγt-IL-17A signaling to delay cardiac aging.

ABSTRACT: New immunosenescence targets for preventing senescence-associated pathological cardiac hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically aged human and mouse samples, the IL-17A level increased with physiological aging, heart failure (HF), and SA-PCH and was negatively correlated with thymic Bmi-1 expression. Bmi-1^f/fLckCre⁺ mice and Bmi-1^f/f littermates were generated to determine whether Bmi-1 delayed T cell aging by maintaining thymic T cell development to prevent SA-PCH. As a result, Bmi-1 promoted thymic T cell development by upregulating Notch signaling and prevented DN1 T cells from differentiating into γδT17 cells by downregulating γδT17 cell differentiation signaling. Bmi-1 upregulated Notch signalin

SUBMITTER: Wang Q 

PROVIDER: S-EPMC12107095 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature