NLRP3 activated macrophages promote endometrial stromal cells migration in endometriosis
NLRP3 activated macrophages promote endometrial stromal cells migration in endometriosis
复制标题
NLRP3激活的巨噬细胞促进子宫内膜异位症中子宫内膜基质细胞的迁移
DOI：
10.1016/j.jri.2022.103649
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发表时间：
2022
影响因子：
3.4
通讯作者：
Yongdong Dai
中科院分区：
文献类型：
--
作者：
Feng Zhou;Fanxuan Zhao;Qianmeng Huang;Xiang Lin;Songying Zhang;Yongdong Dai
Endometriosis (EMs) is a common gynecological disease whose pathogenesis remains unclear. Immunological factors have been a key hotspot in recent years. Peritoneal fluid samples from women with EMs show defectively activated macrophages (MΦs) and strong NOD-like receptor family pyrin domain containing 3 (NLRP3) expression. Activated MΦs secrete interleukin 1β, which stimulates migration of endometrial stromal cells (ESCs) and promotes accumulation of extracellular matrix . Levels of interleukin 1β in peritoneal fluid were significantly higher in patients with stage III-IV EMs compared with stage I-II EMs. We also found that the size and weight of endometrial lesions in NLRP3 -/- mice were significantly lower than those of wild-type mice, and this phenomenon was reversed by intraperitoneally injecting peritoneal MΦs derived from wild-type mice. Moreover, we observed that the NLRP3 inflammasome was activated in MΦs by crosstalk between MΦs and ESCs. Targeted inhibition of NLRP3 significantly reduced lesion development in vivo and suppressed the migration ability of ESCs in vitro. Collectively, these findings suggest that the occurrence of EMs may be associated with the interaction between MΦs and ESCs. • In this study, we found the crosstalk between MΦs and ESCs activates NLRP3 inflammasome, leading to abundant secretion of IL-1β that aggravates ESC migration, and ultimately promote the development of endometriosis. • It revealed that the endometriosis development was closely related to the abdominopelvic cavity microenvironment, and activation of NLRP3 in MΦs drives the occurrence of endometriosis. • Targeted inhibition of NLRP3 significantly reduced lesion development in vivo, and suppressed the migration ability of endometrial stromal cells in vitro. • The study discovered a new pathogenesis mechanism of endometriosis and provided a new therapeutic target for the treatment of endometriosis. In the future research, we will attempt to clarify the mechanism by which NLRP3 pathway on the occurrence and development of endometriosis.
