Elevated interleukin-33, CD1c+ dendritic cells, and interleukin-17A in peritoneal fluid of patients with endometriosis: a case-control study.

BACKGROUND: Endometriosis (EMS) is a chronic inflammatory disorder involving ectopic endometrial tissue growth. This study investigated IL-33, CD1c+ dendritic cells (DCs) and their co-stimulatory molecules (CD40, CD80, CD86), and IL-17 A in the peritoneal fluid (PF) of EMS patients, and explored their interrelationships. METHODS AND RESULTS: PF samples were obtained from 42 women with EMS as experimental subjects and 31 women without EMS as controls. Enzyme-linked immunosorbent assay (ELISA) showed that PF IL-33 (P < 0.001) and IL-17 A (P < 0.01) levels were significantly elevated in EMS patients vs. controls. Moreover, IL-33 levels were significantly higher in stages III-IV than I-II (P < 0.01). Flow cytometry (FCM) revealed no significant difference in the proportion of CD1c + DCs within EMS patient PF compared to controls (P > 0.05). However, the proportions of CD1c+CD40+ (P < 0.001), CD1c+CD80+ (P < 0.05), and CD1c+CD86+ (P < 0.01) DCs were significantly elevated in EMS, with CD1c+CD40 + higher in stages III-IV vs. I-II (P < 0.05). For in vitro experiments, control PF mononuclear cells (PFMCs) were incubated with recombinant IL-33 (100 ng/mL) for 24 h. IL-33 treatment increased IL-17 A production and CD1c+CD40 + and CD1c+CD80 + DC frequences in control PFMCs compared to unstimulated PFMCs (all P < 0.05). CONCLUSION: Elevated IL-33 and IL-17 A levels, along with enhanced CD1c + DC maturation and activation in PF, may contribute to EMS pathogenesis and progression. IL-33 may promote disease development by inducing CD1c + DC maturation/activation, thus increasing IL-17 A production.