Peritoneal cavity-derived GATA6+macrophages inhibit fibrosis through IL33 in endometrium

• DOI: 10.1101/2025.02.02.636170
• Publication Date: 2025-02-08T07:20:29Z
• Authors: Lijie Yin; Jingman Li; Yue Dong; Jiali Wang; Xiuzhu Wang; Yajun Li; Yali Hu; Yayi Hou; Guangfeng Zhao
• Keywords: GATA6; Peritoneal cavity

Macrophages exhibit a high degree of plasticity and play pivotal roles both in the normal physiological cycle endometrium its regeneration following injury. Although some new subsets endometrial macrophages have been identified, their origins functions remain to be further explored. In this study, we employed single-cell sequencing analyze patients with intrauterine adhesion (IUA) caused by We identified unique subset distinguished expression GATA6, marker indicative cavity macrophages. verified that these GATA6+ were large peritoneal (LPMs) migrated from injured endometrium. Upon activation endometrium, LPMs demonstrated increased Interleukin-33 (IL33), mediated Lars-Fos signaling axis, which interacts IL33 enhancer. Moreover, our studies revealed derived inhibited differentiation stromal cells (ESCs) into myofibroblasts, critical step development fibrosis. Furthermore, confirmed inhibitory effect occurred through binding ST2 receptor on ESCs, leading upregulation JMJD3 subsequent suppression myofibroblast differentiation. Our findings highlight essential role promoting repair inhibiting fibrosis IUA.