Interleukin-11 Contributes to TGF-β-induced Fibrotic Responses in Endometriosis

BACKGROUND: Endometriosis is a chronic inflammatory gynecological disorder characterized by progressive fibrosis, yet the mechanisms driving fibrosis remain incompletely understood. This study investigated the role of interleukin-11 (IL-11) in endometriosis-associated fibrosis. METHODS: With informed consent, ovarian endometriotic tissues, cyst fluids, and primary human endometriotic stromal cells (ESCs) were obtained from patients undergoing laparoscopic surgery. Publicly available single-cell RNA sequencing data were analyzed to identify the cellular source of IL11 expression. IL-11 expression was evaluated by immunohistochemistry and ELISA, and its functional role in ESCs was investigated using quantitative PCR, IL-11 neutralization, and collagen gel contraction assays. RESULTS: Single-cell RNA sequencing identified an IL11-high stromal cell population enriched for extracellular matrix remodeling genes. Immunohistochemical analysis demonstrated strong IL-11 expression predominantly localized within fibrotic areas of ovarian endometriotic lesions. In addition, IL-11 concentrations in ovarian endometrioma cyst fluid were significantly higher than those in non-endometriotic ovarian cyst fluid (median: 90.81 vs. 28.91 pg/mL, p < 0.001). In ESCs, TGF-β stimulation significantly increased IL11 mRNA expression (19.2-fold, p < 0.05) and IL-11 secretion (3.7-fold, p < 0.001). IL-11 stimulation also increased the mRNA expression of CTGF (1.4-fold, p = 0.02), PAI-1 (1.3-fold, p = 0.027), and IL-6 (1.4-fold, p = 0.020) in ESCs. Furthermore, IL-11 significantly enhanced collagen gel contraction (relative gel area: 1.00 vs. 0.81, p < 0.05), whereas IL-11 neutralization partially attenuated TGF-β-induced gel contraction (0.46 vs. 0.77, p = 0.063). CONCLUSION: IL-11 acts as a downstream mediator of TGF-β signaling and promotes profibrotic remodeling in endometriotic stromal cells. These findings identify IL-11 as a potential therapeutic target for endometriosis-associated fibrosis.