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.
• The role of immune system aging in BPH pathogenesis remains unclear.

Purpose of the Study:

• To investigate the presence and function of age-associated immune cells in human prostate tissue.
• To determine the correlation between specific immune cell subsets and BPH severity.

Main Methods:

• Analysis of CD8+ T cell subsets in aged human prostates.
• Gene expression profiling for Granzyme K (GZMK) and Granzyme B (GZMB).
• Velocity analysis of CD8+ T cell differentiation in BPH prostates.
• In vitro studies on the effect of granzyme K on prostate fibroblasts.

Main Results:

• An age-associated CD8+ T cell subset (Taa) with high GZMK and low GZMB expression infiltrates aged prostates.
• Taa infiltration positively correlates with International Prostate Symptom Score (IPSS).
• Altered CD8+ T cell differentiation favoring Taa accumulation in larger BPH prostates.
• Granzyme K treatment stimulates pro-inflammatory SASP cytokine secretion from prostate fibroblasts.

Conclusions:

• Age-associated CD8+ T cells expressing Granzyme K contribute to BPH.
• Granzyme K-mediated fibroblast activation promotes immune cell recruitment and activation in the prostate.
• These findings link symptomatic BPH to immune system aging.