Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China.
Gynecol Endocrinol. 2024 Dec;40(1):2411607. doi: 10.1080/09513590.2024.2411607. Epub 2024 Oct 10.
This study aims to explore the alterations of dendritic cells (DCs) subpopulations in ectopic endometrial lesions and unveil the underlying mechanisms.
Patients with endometriosis ( = 81) and women without endometriosis ( = 19) were recruited in this study. Dendritic cells (DCs) in the endometrial samples were counted after immunohistochemistry staining. The proportion of myeloid DCs and plasmacytoid DCs was calculated by flow cytometry. Primary DCs were isolated from tissues, and the cell viability and apoptosis were examined by MTT assay and flow cytometry. Cytokines were detected by the enzyme-linked immunosorbent assay. Differentially expressed genes were filtered by analyzing two datasets that were downloaded from GEO database and detected by RT-qPCR in tissues and isolated DCs. The function of HSD11B1 was examined in an endometrial stromal cell-DCs co-culture system and cultured DCs.
Reduced myeloid DCs and increased CD11c-CD304-DCs were found in ectopic endometrium compared to control endometrium and eutopic endometrium from endometriosis patients. Myeloid DCs isolated from ectopic endometrium expressed less CD80, CD83, CD86 and had reduced proliferation, increased apoptosis, and reduced cytokine production. The expression of HSD11B1 was significantly increased in both ectopic endometrium and isolated myeloid DCs. Overexpression of HSD11B1 in immature DCs could repress DCs maturation and cytokine production. Endometrial stromal cells overexpressing HSD11B1 secreted increased cortisol, which repressed DCs maturation.
HSD11B1 is upregulated in ectopic endometrial lesions, which may contribute to endometriosis through repressing myeloid DCs maturation.
本研究旨在探讨异位子宫内膜病变中树突状细胞（DC）亚群的变化，并揭示其潜在机制。
本研究纳入了 81 例子宫内膜异位症患者和 19 例非子宫内膜异位症患者。通过免疫组织化学染色计数子宫内膜样本中的树突状细胞（DC）。通过流式细胞术计算髓样 DC 和浆细胞样 DC 的比例。从组织中分离原代 DC，通过 MTT 检测和流式细胞术检测细胞活力和凋亡。通过酶联免疫吸附试验检测细胞因子。通过分析从 GEO 数据库下载的两个数据集并在组织和分离的 DC 中通过 RT-qPCR 检测来筛选差异表达基因。在子宫内膜基质细胞-DC 共培养系统和培养的 DC 中检测 HSD11B1 的功能。
与对照组子宫内膜和子宫内膜异位症患者的在位子宫内膜相比，异位子宫内膜中发现髓样 DC 减少，CD11c-CD304-DC 增加。从异位子宫内膜分离的髓样 DC 表达较少的 CD80、CD83、CD86，增殖减少，凋亡增加，细胞因子产生减少。HSD11B1 在异位子宫内膜和分离的髓样 DC 中的表达均显著增加。不成熟 DC 中 HSD11B1 的过表达可抑制 DC 成熟和细胞因子产生。过表达 HSD11B1 的子宫内膜基质细胞分泌增加的皮质醇，抑制 DC 成熟。
HSD11B1 在异位子宫内膜病变中上调，可能通过抑制髓样 DC 成熟而导致子宫内膜异位症。
