Broman Meaghan M, Lanman Nadia A, Vickman Renee E, Cresswell Gregory M, Kothandaraman Harish, Kolliegbo Andree, Paez Juan Sebastian Paez, Glaser Alexander P, Helfand Brian T, Henry Gervaise, Strand Douglas W, Franco Omar E, Hayward Simon W, Ratliff Timothy L
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, United States.
Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN, United States.
Front Immunol. 2025 Jul 7;16:1585446. doi: 10.3389/fimmu.2025.1585446. eCollection 2025.
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.
scRNA-seq data from immune cells isolated from small (≤40g) and large (≥90g) prostates from aged men (>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.
An age-associated CD8 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 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.
良性前列腺增生（BPH）是男性中最常见的与年龄相关的疾病之一。随着年龄增长与BPH同时出现，常观察到前列腺免疫细胞浸润；然而，免疫细胞中与年龄相关的变化对BPH的作用尚不清楚。由于T细胞是老年前列腺中的主要免疫细胞，因此推测T细胞亚群中与年龄相关的改变导致了BPH症状。
将从老年男性（>50岁）的小前列腺（≤40g）和大前列腺（≥90g）中分离出的免疫细胞的单细胞RNA测序（scRNA-seq）数据与先前发表的来自三个年轻器官供体前列腺的scRNA-seq数据相结合，以比较年轻与老年前列腺T细胞以及老年前列腺中小与大的T细胞。用颗粒酶K处理增殖和衰老的BPH患者来源的成纤维细胞，并通过酶联免疫吸附测定（ELISA）测量与衰老相关的分泌表型（SASP）相关的细胞因子。
一个与年龄相关的CD8 T细胞亚群（Taa），其颗粒酶K（GZMKhi）基因表达高而颗粒酶B（GZMBlow）基因表达低，浸润老年人类前列腺，且与国际前列腺症状评分（IPSS）呈正相关。速度分析表明，与年龄匹配的小前列腺相比，大BPH前列腺中CD8 T细胞分化发生改变，有利于Taa积累。体外对人BPH患者来源的大前列腺成纤维细胞进行颗粒酶K处理可增加促炎衰老相关分泌表型（SASP）相关细胞因子的分泌。
这些数据表明，颗粒酶K介导的对前列腺基质成纤维细胞SASP细胞因子和趋化因子产生的刺激促进了前列腺免疫细胞的募集和激活。总体而言，这些结果将有症状的BPH与免疫衰老联系起来。
