Single‐Cell Sequencing Reveals That CD4⁺ T Cells Eliminate Senescent Prostate Epithelium to Delay Progression of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is an age‐related condition characterized by progressive prostate enlargement driven in part by the accumulation of senescent epithelial cells and their pro‐inflammatory secretome. Using human single‐cell RNA sequencing and laser capture microdissection, we identified C‐X‐C Motif Chemokine Ligand 13 (CXCL13) as a key chemokine secreted by senescent prostate epithelial cells. CXCL13 recruits CD4 + T cells via the C‐X‐C Chemokine Receptor Type 5 (CXCR5) receptor, facilitating immune recognition through human leukocyte antigen–DR isotype (HLA‐DR) and promoting senescent cell clearance. Functional assays revealed that CD4 + cytotoxic T lymphocytes (CTLs) mediate this clearance, while regulatory T cells (Tregs) suppress it, forming a functional dichotomy. Immunohistochemistry, transwell migration, and co‐culture assays confirmed this CXCL13–CXCR5–HLA‐DR axis. In a testosterone‐induced BPH mouse model, CXCL13 treatment enhanced CD4 + T cell infiltration and reduced epithelial senescence, while CD4 + T cell depletion reversed these effects. Single‐cell transcriptomics in mice further validated increased CXCL13 expression and CD4 + T cell engagement. These findings uncover a critical immune surveillance mechanism in BPH and suggest that targeting the CXCL13–CD4 + T cell axis may offer a novel therapeutic strategy for age‐related prostate enlargement.