Harnessing the CD16-PI3Kγ axis in peritoneal CD14hi macrophages: A transformative approach to endometriosis management

Wei C, Chunyan Wei, Liu Y, Yukai Liu, Chen S, Siman Chen, Mingqing Li, Li M, Ming‐Qing Li, Li D, Dajin Li, Da‐Jin Li, Xiaoyong Zhu, Zhu X, Zhang X, Xiaoping Zhang
International journal of biological macromolecules · 2025 · vol. 322(Pt 1) , pp. 146627 · doi:10.1016/j.ijbiomac.2025.146627 · PMID:40780336 · W4413008109
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study investigated targeting the CD16-PI3Kγ axis in peritoneal CD14hi macrophages as a potential therapeutic strategy for endometriosis.

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Abstract

Endometriosis (EMS) is a prevalent estrogen-dependent gynecological disorder characterized by ectopic growth of endometrial tissue. Central to its pathophysiology, peritoneal CD14hi macrophages exhibit a pro-EMS phenotype and drive disease progression. These macrophages originate from CD16-CD14+ monocytes and co-express functional surface markers critical for EMS development. We demonstrate that endometrial stromal cells (ESCs) exert significantly stronger regulatory effects on CD14hi macrophage polarization than estrogen alone. Crucially, CD16 maintains peritoneal CD14hi macrophage homeostasis in ovarian EMS. To investigate CD16's role in vivo, we established a novel EMS mouse model (WH-EMS) by intraperitoneal grafting of wild-type uterine tissues into FcγRIII-/- (CD16-deficient) female mice. Within this model, peritoneal FcγRIII- macrophages exhibited impaired immunocompetence (diminished CD80 and IL4 expression), whereas macrophages infiltrating ectopic lesions displayed pronounced immune tolerance (elevated IL-4 expression). Pharmacologically targeting CD16 downstream signaling, PI3Kγ inhibition via IPI-549 attenuated ESC-induced differentiation of both CD14hi and CD14low macrophages in vitro, ultimately ameliorating pathological conditions in WH-EMS mice. This cumulative evidence indicates that CD14hi macrophages promote EMS progression through CD16-dependent mechanisms. Consequently, therapeutic targeting of CD16 or its downstream effectors (e.g., PI3Kγ) represents a promising strategy for clinical EMS management.

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Condition tags

endometriosis

MeSH descriptors

Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase Class Ib Phosphatidylinositol 3-Kinase

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 (51)

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