The Prostate · 2026
Identification of Novel CD52+ Fibroblasts in Nodular Prostatic Hyperplasia.
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Strobel Oliver R, Xia Hanyu, Ropa James P, Strand Douglas W, Jerde Travis J, Arrizabalaga Gustavo
Аннотация
BACKGROUND: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms are strongly associated with chronic prostate inflammation and stromal remodeling, yet the stromal cell programs that emerge during inflammatory, nodular remodeling remain incompletely defined. A Toxoplasma gondii infection model produces persistent inflammation and nodular formations, providing an experimentally tractable system to map inflammation-linked stromal states.
METHODS: We performed single-cell RNA sequencing of prostates from control and chronically infected male CBA/J mice harvested at 28 days post-infection (DPI). Stromal subset reprogramming was assessed by cluster-resolved pseudobulk differential expression and Ingenuity Pathway Analysis. Stromal expansion and Cd52+ fibroblast subset changes were validated by whole-section immunofluorescence at 28 and 60 DPI using a CellposeSAM-based tissue cytometry pipeline. To assess human relevance, CD52+ fibroblasts were evaluated in FFPE human prostate sections by comparing inflamed versus non-inflamed stromal regions.
RESULTS: Whole-prostate single-cell profiling resolved stromal, epithelial, immune, and seminal vesicle compartments. Infection increased immune-cell abundance and increased stromal representation among non-immune cells (53.1% in controls to 69.0% in infected prostates). Stromal reclustering identified eight subsets, including a Cd52+/Ccl5+ immune-reactive fibroblast population that showed the strongest selective expansion during infection. Whole-section imaging supported overall stromal expansion over time, and Cd52+ fibroblasts were higher during infection at 60 DPI (270% increase, p = 0.0507), whereas Cxcl13+ fibroblasts remained rare and stable across conditions. Pathway analysis indicated immune-like stromal reprogramming during infection, with antigen-presentation programs enriched in larger fibroblast subsets and interferon/JAK-STAT signaling most consistently concentrated in the Cd52+/Ccl5+ subset. In human prostate tissue, CD52+ VIM+ CD45- fibroblasts were significantly enriched in inflamed regions compared with paired non-inflamed regions within the same specimen (paired Wilcoxon p = 0.0026).
CONCLUSIONS: Chronic, pathogen-driven inflammation produces selective, program-specific stromal remodeling rather than uniform fibroblast activation. An interferon-reactive Cd52+ fibroblast state expands during infection in mice and marks inflamed stromal microenvironments in human prostate, supporting discrete immune-reactive fibroblast programs as a prominent feature of inflammation-associated prostate remodeling.
METHODS: We performed single-cell RNA sequencing of prostates from control and chronically infected male CBA/J mice harvested at 28 days post-infection (DPI). Stromal subset reprogramming was assessed by cluster-resolved pseudobulk differential expression and Ingenuity Pathway Analysis. Stromal expansion and Cd52+ fibroblast subset changes were validated by whole-section immunofluorescence at 28 and 60 DPI using a CellposeSAM-based tissue cytometry pipeline. To assess human relevance, CD52+ fibroblasts were evaluated in FFPE human prostate sections by comparing inflamed versus non-inflamed stromal regions.
RESULTS: Whole-prostate single-cell profiling resolved stromal, epithelial, immune, and seminal vesicle compartments. Infection increased immune-cell abundance and increased stromal representation among non-immune cells (53.1% in controls to 69.0% in infected prostates). Stromal reclustering identified eight subsets, including a Cd52+/Ccl5+ immune-reactive fibroblast population that showed the strongest selective expansion during infection. Whole-section imaging supported overall stromal expansion over time, and Cd52+ fibroblasts were higher during infection at 60 DPI (270% increase, p = 0.0507), whereas Cxcl13+ fibroblasts remained rare and stable across conditions. Pathway analysis indicated immune-like stromal reprogramming during infection, with antigen-presentation programs enriched in larger fibroblast subsets and interferon/JAK-STAT signaling most consistently concentrated in the Cd52+/Ccl5+ subset. In human prostate tissue, CD52+ VIM+ CD45- fibroblasts were significantly enriched in inflamed regions compared with paired non-inflamed regions within the same specimen (paired Wilcoxon p = 0.0026).
CONCLUSIONS: Chronic, pathogen-driven inflammation produces selective, program-specific stromal remodeling rather than uniform fibroblast activation. An interferon-reactive Cd52+ fibroblast state expands during infection in mice and marks inflamed stromal microenvironments in human prostate, supporting discrete immune-reactive fibroblast programs as a prominent feature of inflammation-associated prostate remodeling.