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Lupus susceptibility gene Esrrg modulates regulatory T cells through mitochondrial metabolism, 2021, Li et al

Discussion in 'Other health news and research' started by Andy, Jun 23, 2021.

  1. Andy

    Andy Committee Member

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    Abstract.

    Estrogen-related receptor gamma (Esrrg) is a murine lupus susceptibility gene associated with T cell activation. Here, we report that Esrrg controls regulatory T cells (Treg) through mitochondria homeostasis. Esrrg deficiency impaired the maintenance and function of Treg cells, leading to global T cell activation and autoimmunity in aged mice. Further, Esrrg-deficient Treg cells presented an impaired differentiation into follicular Treg (Tfr) cells that enhanced follicular helper T cells (Tfh) responses. Mechanistically, Esrrg-deficient Treg cells presented with dysregulated mitochondria with decreased oxygen consumption as well as ATP and NAD+ production. In addition, Esrrg-deficient Treg cells exhibited decreased phosphatidylinositol and TGF-β signaling pathways and increased mTORC1 activation. We found that the expression of human ESRRG, which is high in Treg cells, was lower in CD4+ T cells from lupus patients than in healthy controls. Finally, knocking down ESRRG in Jurkat T cells decreased their metabolism. Together, our results reveal a critical role of Esrrg in the maintenance and metabolism of Treg cells, which may provide a genetic link between lupus pathogenesis and mitochondrial dysfunction in T cells.

    Open access, https://insight.jci.org/articles/view/143540
     
    leokitten, Hutan, Ariel and 1 other person like this.

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