Enriched and highly functional mucosal-associated invariant T cells in follicular fluid of patients with polycystic ovary syndrome

Abstract Background The involvement of mucosal-associated invariant T (MAIT) cells in polycystic ovary syndrome (PCOS) has not been adequately studied, and their potential as therapeutic targets remains unexplored. In this study, we investigated the immune profile of MAIT cells in the localized ovarian inflammatory milieu of patients with PCOS and explored their association with the inflammatory manifestations of this condition. Methods Follicular fluid samples were obtained from 20 patients with PCOS and 18 controls (women with male-factor infertility) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between May and December 2023. Paired peripheral blood samples were collected before oocyte retrieval. Mononuclear cells were isolated from both compartments, and flow cytometry was used to assess MAIT cell frequency, phenotype, and cytokine production. Correlations with clinical parameters were also evaluated. Results Circulating MAIT cells from patients with PCOS showed a reduced frequency but exhibited an activated phenotype characterized by elevated of CD38, PD-1, and TIGIT expression. Notably, MAIT cells were enriched in the follicular fluid of patients with PCOS, where they expressed high levels of PD-1 and CD38 and secreted higher amounts of IFN-γ and IL-17A, suggesting the presence of both MAIT1 and MAIT17 subsets within the ovarian inflammatory milieu. Conclusions MAIT cells are enriched in the follicular fluid of patients with PCOS and display an activated, proinflammatory phenotype with enhanced IFN-γ and IL-17A production. The correlations between MAIT cell parameters and AMH and BMI, together with the association between MAIT cell-derived IL-17A and testosterone, suggest a potential link between the local enrichment of MAIT cells and the inflammatory and hormonal milieu in PCOS, although the directionality of these associations remains to be determined.