{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:07:04Z","timestamp":1792750024694,"version":"4.5.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Benign prostatic hyperplasia (BPH) is among the most common age-associated diseases in men. Prostatic immune cell infiltration is frequently observed with aging coincident with BPH; however, the contribution of age-related changes in immune cells to BPH is not clear. As T cells are the predominate immune cell in aged prostates, it is hypothesized that age-associated alterations in T cell subsets contribute to BPH symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>scRNA-seq data from immune cells isolated from small (\u226440g) and large (\u226590g) prostates from aged men (&amp;gt;50 years) were combined with previously published scRNA-seq data from three young organ donor prostates to compare young to aged prostate T cells and small to large aged prostate T cells. Cycling and senescent BPH patient-derived fibroblasts were treated with granzyme K and senescence-associated secretory phenotype (SASP)-associated cytokines were measured by ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An age-associated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell subset (Taa) with high Granzyme K (GZMKhi) and low Granzyme B (GZMBlow) gene expression infiltrated aged human prostates and positively correlated with International Prostate Symptom Score (IPSS). A velocity analysis indicated that CD8\n                      <jats:sup>+<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1585446","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:11:58Z","timestamp":1751886718000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Immune cell single-cell RNA sequencing analyses link an age-associated T cell subset to symptomatic benign prostatic hyperplasia"],"prefix":"10.3389","volume":"16","author":[{"given":"Meaghan M.","family":"Broman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia A.","family":"Lanman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee E.","family":"Vickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory 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