An Age-Associated T-Cell Population Linked to Benign Prostate Hyperplasia
Benign prostate hyperplasia is a common aspect of aging in men, an enlargement of the prostate over time that occurs for underlying reasons that remain incompletely understood. Given too much enlargement the condition becomes far from benign, as it can interrupt the ability to urinate. It also appears to increase the risk of later prostate cancer. Empirically, various medications and lifestyle changes seem to help in some patients, but reliable prevention and reversal of the condition remains out of reach.
In today's preprint paper, researchers provide evidence linking a subpopulation of T cells that arises with age to the development of benign prostate hyperplasia, implying a link to immune aging. This is particularly interesting in the context that prior infection and inflammation of the prostate (known as prostatitis) has been shown to increase the risk of later benign prostate hyperplasia. There is also the suggestion that this can be tied in to the presence and activity of senescent cells present in the aged prostate, with the T cells encouraging greater bad behavior on the part of senescent cells.
Benign prostatic hyperplasia (BPH) is among the most common age-associated diseases in men; however, the contribution of age-related changes in immune cells to BPH is not clear. The current study determined that an age-associated CD8+ T cell subset (Taa) with high Granzyme K (GZMKhi) and low Granzyme B (GZMBlow) gene expression 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, favoring Taa accumulation. In vitro granzyme K treatment of human BPH patient-derived large prostate fibroblasts increased secretion of pro-inflammatory senescence-associated secretory phenotype (SASP)-associated cytokines. This data suggests 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.