Research ArticleImmunology

The lysine deacetylase Sirtuin 1 modulates the localization and function of the Notch1 receptor in regulatory T cells

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Sci. Signal.  04 Apr 2017:
Vol. 10, Issue 473, eaah4679
DOI: 10.1126/scisignal.aah4679

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Another Notch in the belt for Sirt1

Regulatory T (Treg) cells suppress effector T cell function to prevent autoimmunity. Cell-based therapies to treat autoimmune diseases are effective only if Treg cells survive and are functional after being transferred to patients. Marcel et al. investigated how Notch signaling protects Treg cells from apoptosis induced by cytokine withdrawal. The enzyme SIRT1 deacetylated NIC, the intracellular domain of the Notch receptor, which retained NIC in the cytosol where it promoted anti-apoptotic signaling. In mouse models of inflammation, deletion of Sirt1 or Notch1 decreased Treg cell survival and exacerbated inflammatory disease. Together, these data suggest that the Sirt1-Notch signaling axis may be targeted therapeutically to manipulate Treg cell survival.