RRC ID 67583
Author Jiao X, Zhang X, Li N, Zhang D, Zhao S, Dang Y, Zanvit P, Jin W, Chen ZJ, Chen W, Qin Y.
Title Treg deficiency-mediated TH 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells.
Journal Clin Transl Med
Abstract Immune dysregulation has long been proposed as a component of premature ovarian insufficiency (POI), but the underlying mediators and mechanisms remain largely unknown. Here we showed that patients with POI had augmented T helper 1 (TH 1) responses and regulatory T (Treg ) cell deficiency in both the periphery and the ovary compared to the control women. The increased ratio of TH 1:Treg cells was strongly correlated with the severity of POI. In mouse models of POI, the increased infiltration of TH 1 cells in the ovary resulted in follicle atresia and ovarian insufficiency, which could be prevented and reversed by Treg cells. Importantly, interferon (IFN) -γ and tumor necrosis factor (TNF) -α cooperatively promoted the apoptosis of granulosa cells and suppressed their steroidogenesis by modulating CTGF and CYP19A1. We have thus revealed a previously unrecognized Treg cell deficiency-mediated TH 1 response in the pathogenesis of POI, which should have implications for therapeutic interventions in patients with POI.
Volume 11(6)
Pages e448
Published 2021-6-1
DOI 10.1002/ctm2.448
PMID 34185428
PMC PMC8214854
MeSH Adult Animals Apoptosis* Female Granulosa Cells / immunology Granulosa Cells / metabolism Granulosa Cells / pathology* Humans Interferon-gamma / metabolism Mice Mice, Inbred C57BL Primary Ovarian Insufficiency / etiology Primary Ovarian Insufficiency / metabolism Primary Ovarian Insufficiency / pathology* Steroids / biosynthesis* T-Lymphocytes, Regulatory / immunology* Th1 Cells / immunology* Tumor Necrosis Factor-alpha / metabolism
Human and Animal Cells KGN(RCB1154)