Niclosamide targets macrophages to rescue the disrupted peritoneal homeostasis in endometriosis

Liang Zhao, Mingxin Shi, Sarayut Winuthayanon, James A. MacLean, Kanako Hayashi
In: bioRxiv · 2022 · doi:10.1101/2022.04.05.487220 · W4224244712
preprint OA: green CC0
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Niclosamide rescues peritoneal homeostasis in endometriosis by regulating macrophage differentiation, replenishment, and ablation, and reversing disrupted macrophage-B cell communication.

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Abstract

Abstract Due to the vital roles of macrophages in the pathogenesis of endometriosis, targeting macrophages could be a new therapeutic direction. Here, we investigated the efficacy of niclosamide for the resolution of perturbed microenvironment caused by dysregulated macrophages in a mouse model of endometriosis. Single-cell transcriptomic analysis revealed the heterogeneity of macrophage subpopulations including three newly identified 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 ablation of embryo-derived LPMs, which were stepwise suppressed by niclosamide. In addition, niclosamide reversed intercellular communications between macrophages and B cells which were disrupted by ELL. Therefore, niclosamide rescued the perturbed microenvironment in endometriosis through its fine regulations on the dynamic progression of macrophages and could be a new promising therapy for endometriosis. Summary Niclosamide tunes the dynamic progression of peritoneal macrophages and their intercellular communications with B cells to rescue the disrupted microenvironment in the peritoneal cavity in a mouse model of endometriosis. Graphic Abstract

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Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (57)

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