| First Author | Marcel N | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27267497 | Mgi Jnum | J:234085 |
| Mgi Id | MGI:5789049 | Doi | 10.7554/eLife.14023 |
| Citation | Marcel N, et al. (2016) Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells. Elife 5:e14023 |
| abstractText | Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1(-/-) Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation. |
