Niclosamide targets the dynamic progression of macrophages for the resolution of endometriosis in a mouse model

• Published in: Communications biology Vol. 5; no. 1; pp. 1225 - 16
• Main Authors: Zhao, Liang, Shi, Mingxin, Winuthayanon, Sarayut, MacLean, James A., Hayashi, Kanako
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 38/39; 631/443/494/2732/2730; 64/60; 692/699/2732/2730; 96/1; Animals; Biology; Biomedical and Life Sciences; Disease Models, Animal; Endometriosis; Endometriosis - drug therapy; Female; Humans; Life Sciences; Lymphocytes B; Macrophages; Macrophages - pathology; Macrophages, Peritoneal - pathology; Mice; Microenvironments; Niclosamide; Niclosamide - pharmacology; Niclosamide - therapeutic use; Pathogenesis; Peritoneum; Transcriptomics
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-04211-0

Due to the vital roles of macrophages in the pathogenesis of endometriosis, targeting macrophages could be a promising therapeutic direction. Here, we investigated the efficacy of niclosamide for the resolution of a perturbed microenvironment caused by dysregulated macrophages in a mouse model of endometriosis. Single-cell transcriptomic analysis revealed the heterogeneity of macrophages including three intermediate subtypes with sharing characteristics of traditional “small” or “large” peritoneal macrophages (SPMs and LPMs) in the peritoneal cavity. Endometriosis-like lesions (ELL) enhanced the differentiation of recruited macrophages, promoted the replenishment of resident LPMs, and increased the ablation of embryo-derived LPMs, which were stepwise suppressed by niclosamide. In addition, niclosamide restored intercellular communications between macrophages and B cells. Therefore, niclosamide rescued the perturbed microenvironment in endometriosis through its fine regulations on the dynamic progression of macrophages. Validation of similar macrophage pathogenesis in patients will further promote the clinical usage of niclosamide for endometriosis treatment. In a mouse model of endometriosis, niclosamide is found to have potential therapeutic value through its fine regulations of the dynamic progression of macrophages.