■子宫内膜异位症(EM)是一种慢性雌激素依赖性疾病,其特征是子宫外子宫内膜样组织的生长,对育龄妇女构成重大负担。先前的研究表明,EM患者的肠道微生物群失调与白细胞介素-17A(IL-17A)之间存在相关性。IL-17A,一个有前途的免疫调节分子,在人体生理学中发挥双重作用,驱动炎性疾病。然而,IL-17A在EM中的功能和起源仍然缺乏表征。
■采用单细胞数据分析来表征EM病变中的IL-17A活性。进行粪便菌群移植以探讨肠道菌群对EM的影响。通过16SrRNA测序和靶向代谢组学评估肠道微生物群和胆汁酸代谢。使用流式细胞术测量Th17细胞比例。
■在EM病变内的骨髓细胞亚群中观察到IL-17受体A(IL-17RA)的高表达,并且可能与病变中炎性细胞的迁移和募集有关。在EM患者的腹膜液和卵泡液中进一步验证了IL-17A水平的升高。胆汁酸水平失调,特别是升高的鹅去氧胆酸(CDCA)和熊去氧胆酸(UDCA),在EM小鼠模型的肠道和腹膜液中发现。额外的CDCA给药减少了EM损伤并调节了Th17细胞比例,而UDCA无明显影响。
■我们的发现揭示了IL-17A在EM中的起源和功能,涉及病变迁移和募集。胆汁酸代谢失调可能有助于EM发病机理,CDCA表现出治疗潜力。
UNASSIGNED: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized.
UNASSIGNED: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry.
UNASSIGNED: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects.
UNASSIGNED: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.