Immune cell single-cell RNA sequencing analyses link an age-associated T cell subset to symptomatic benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is among the most common age-associated diseases in men. Whether age-related changes in immune cells, termed immunosenescence, contribute to BPH is not clear. Specific T cell populations, in particular a subset of CD8+ T cells with high Granzyme K (GZMKhi) and low Granzyme B (GZMBlow) gene expression, have been associated with aging; however, the precise function and biological significance of these cells in age-related diseases is not known. The current study determine that Taa cells infiltrate aged human prostates and positively correlate with International Prostate Symptom Score (IPSS). A velocity analysis indicated that CD8+ T cell differentiation is altered in large BPH prostates compared to small age-matched prostates. In vitro granzyme K treatment of human BPH patient-derived large prostate fibroblasts increased secretion of senescence-associated secretory phenotype (SASP)-associated cytokines. These data suggest that granzyme K-mediated stimulation of prostate stromal fibroblast SASP cytokine and chemokine production promotes prostate immune cell recruitment and activation. Overall, these results connect symptomatic BPH with immune aging. For aged prostate tissues, transitional zone (TZ) tissue was excised from each collected large (≥90 grams) and small (≤40 grams) prostates. Tissues were digested and RNA was extracted. Poly A selection was employed to capture mRNA transcripts, which were then sequenced by Novogene. Bulk RNA-seq paired-end 150 bp reads were sequenced by Novogene.