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

Broman, M.; Lanman, N. A.; Vickman, R. E.; Cresswell, G.; Kothandaraman, H.; Kolliegbo, A.; Paez Paez, J. S.; Glaser, A. P.; Helfand, B. T.; Henry, G.; Strand, D.; Franco, O.; Crawford, S.; Hayward, S. W.; Ratliff, T.

doi:10.1101/2024.12.30.629739

bioRxiv · 10.1101/2024.12.30.629739

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

Broman, M.·Lanman, N. A.·Vickman, R. E.·Cresswell, G.·Kothandaraman, H.·Kolliegbo, A.·Paez Paez, J. S.·Glaser, A. P.·Helfand, B. T.·Henry, G.·Strand, D.·Franco, O.·Crawford, S.·Hayward, S. W.·Ratliff, T.

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Abstract

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. 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.

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Broman, M., Lanman, N. A., Vickman, R. E., Cresswell, G., Kothandaraman, H., Kolliegbo, A., Paez Paez, J. S., Glaser, A. P., Helfand, B. T., Henry, G., Strand, D., Franco, O., Crawford, S., Hayward, S. W., Ratliff, T.. 2024-12-30. Immune cell single-cell RNA sequencing analyses link an age-associated T cell subset to symptomatic benign prostatic hyperplasia. https://doi.org/10.1101/2024.12.30.629739

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