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

Area of Science:

• Immunology
• Urology
• Gerontology

Background:

• Benign prostatic hyperplasia (BPH) is a common age-related condition in men.
• Immune cell infiltration, particularly T cells, is observed in aged prostates, but their role in BPH is unclear.
• This study investigates the contribution of age-associated T cell alterations to BPH pathogenesis.

Purpose of the Study:

• To compare T cell subsets in young, aged, and BPH-affected prostates.
• To identify specific T cell populations associated with BPH severity.
• To elucidate the mechanism by which T cells influence prostate stromal cells in BPH.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of prostate immune cells from young and aged men.
• Analysis of T cell differentiation and gene expression in small versus large aged prostates.
• In vitro experiments treating human BPH fibroblasts with granzyme K to assess cytokine secretion.

Main Results:

• A distinct age-associated T cell subset (Taa) characterized by high Granzyme K (GZMKhi) and low Granzyme B (GZMBlow) was identified in aged prostates.
• Taa accumulation correlated positively with International Prostate Symptom Score (IPSS), a measure of BPH severity.
• Granzyme K treatment induced pro-inflammatory senescence-associated secretory phenotype (SASP) cytokines in BPH fibroblasts, suggesting a mechanism for immune cell recruitment.

Conclusions:

• Age-associated T cells expressing high Granzyme K contribute to BPH pathogenesis.
• Granzyme K-mediated fibroblast activation and SASP cytokine production promote prostate inflammation and immune cell infiltration.
• These findings link symptomatic BPH to the aging immune system and suggest potential therapeutic targets.