Identification of novel CD52+ fibroblasts in nodular prostatic hyperplasia

To assess human relevance, CD52⁺ fibroblasts were evaluated in FFPE human prostate sections by comparing inflamed versus non-inflamed stromal regions. 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 increased during infection (trend at 28 DPI; borderline significance 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).

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.