NLRC5通过抑制ERβ介导的炎症反应发挥抗子宫内膜异位症作用

子宫内膜异位症被公认为一种慢性炎症性疾病。其发生发展受雌激素受体β（ERβ）影响很大，而NOD样受体（NLR）家族含CARD结构域的蛋白NLRC5在子宫内膜异位症中表现出抗炎作用。然而，NLRC5介导的抗炎作用是否涉及ERβ介导的子宫内膜异位症，仍不明确。本研究旨在探讨这一关系。收集了10例子宫内膜异位症患者的子宫腔内正常内膜和异位内膜组织，以及10例健康育龄妇女的子宫内膜样本，采用免疫组化（IHC）方法分析ERβ的表达水平。随后，我们通过腹腔注射建立小鼠子宫内膜异位症模型，检测ERβ、NLRC5、肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-6和IL-10的表达，并测量子宫内膜异位病变的体积。在体外实验中，将人子宫内膜间质细胞（hESCs）分别转染ERβ过表达和NLRC5过表达质粒，利用定量实时PCR（qRT-PCR）和Western印迹分析检测ERβ和NLRC5的表达。同时，通过酶联免疫吸附（ELISA）检测细胞培养上清中的TNF-α、IL-6和IL-10浓度。此外，采用Transwell和伤口愈合实验评估hESCs的迁移和侵袭能力。NLRC5表达的抑制促进了小鼠异位病变的发展，上调促炎因子TNF-α和IL-6的表达，下调抗炎因子IL-10的水平。子宫内膜异位症中NLRC5的高表达依赖于ERβ的过表达。ERβ部分依赖炎症微环境促进hESCs的迁移。最后，NLRC5过表达抑制了ERβ介导的子宫内膜异位症的发生和炎症反应。研究结果表明，先天免疫分子NLRC5介导的抗炎作用参与了ERβ介导的子宫内膜异位症的发生机制，部分阐明了子宫内膜异位症的病理机制，丰富了我们对炎症反应相关特定分子的认识，并可能为子宫内膜异位症提供新的治疗靶点。

Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation.Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays.Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis.Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis.