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. Overall design: 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.