T reg deficiency‐mediated T H 1 response causes human premature ovarian insufficiency through apoptosis and steroidogenesis dysfunction of granulosa cells
Autor: | Xiruo Zhang, Nianyu Li, Wenwen Jin, Yujie Dang, Xue Jiao, Peter Zanvit, Zi-Jiang Chen, Wanjun Chen, Yingying Qin, Shidou Zhao, Dunfang Zhang |
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Rok vydání: | 2021 |
Předmět: |
Adult
0301 basic medicine Medicine (General) steroidogenesis Cell Medicine (miscellaneous) Ovary Primary Ovarian Insufficiency Premature ovarian insufficiency medicine.disease_cause T-Lymphocytes Regulatory Interferon-gamma Mice 03 medical and health sciences R5-920 0302 clinical medicine Interferon medicine Animals Humans Research Articles Granulosa Cells Tumor Necrosis Factor-alpha business.industry POI apoptosis Th1 Cells Immune dysregulation TH1 Mice Inbred C57BL CTGF 030104 developmental biology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Cancer research Molecular Medicine Female Steroids Tumor necrosis factor alpha business Treg cells Research Article medicine.drug |
Zdroj: | Clinical and Translational Medicine Clinical and Translational Medicine, Vol 11, Iss 6, Pp n/a-n/a (2021) |
ISSN: | 2001-1326 |
Popis: | 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 (TH1) responses and regulatory T (Treg) cell deficiency in both the periphery and the ovary compared to the control women. The increased ratio of TH1:Treg cells was strongly correlated with the severity of POI. In mouse models of POI, the increased infiltration of TH1 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 TH1 response in the pathogenesis of POI, which should have implications for therapeutic interventions in patients with POI. The Treg cells deficiency with decreased number and impaired suppression function mediate augmented TH1 responses in premature ovarian insufficiency (POI). The increased TH1 proinflammatory cytokines IFN‐γ and TNF‐α impair steroidogenesis by targeting CYP19A1 and promote apoptosis of granulosa cells partially by down‐regulation of CTGF via JAK‐STAT1 and NF‐κB activation, hence contribute to follicle atresia, ovarian dysfunction and premature insufficiency. |
Databáze: | OpenAIRE |
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