Chronic prostatitis and Pelvic Pain syndrome (CP/CPPS) is an autoimmune inflammatory disease characterized by pelvic or perineal pain and infiltration of inflammatory cells in the prostate. C-X-C chemokine receptor type 7 (CXCR7) is an atypical chemokine receptor that has been shown to play a key role in inflammatory processes in prostate cancer. However, the role of CXCR7 in autoimmune prostate and immune regulation in CP/CPPS along with the mechanism of action for CXCR7 remains unclear. In this study, a mouse model of experimental autoimmune prostatitis (EAP) was constructed by subcutaneous injection of antigen, and CXCR7 agonist was administered to investigate the effects of CXCR7 on the proportion of immune cells and fibrosis in CP/CPPS. Western blotting, immunohistochemical staining and immunofluorescence, flow cytometry, and masson's trichrome staining were used to study the regulatory mechanisms of CXCR7 in immune regulation. CXCR7 agonists can significantly reduce pain and prostatic inflammation, and in vivo flow cytometry studies showed that the antagonists restored the imbalance of the Th17/Treg cell ratio. To elucidate the potential mechanisms by which CXCR7 influences the pathogenesis of CP/CPPS, we conducted simultaneous RNA-seq and non-targeted metabolome sequencing. Our findings suggest that CXCR7 agonists alleviate fibrosis in autoimmune prostatitis by inhibiting the TGFβ/SMAD pathway. This study provides the foundation to target the immunological function of CXCR7 as a novel therapy for CP/CPPS.
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http://dx.doi.org/10.1016/j.intimp.2024.113685 | DOI Listing |
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