Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
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- Nimi Marcel
- National Centre for Biological Sciences, Bengaluru, India
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- Apurva Sarin
- National Centre for Biological Sciences, Bengaluru, India
書誌事項
- 公開日
- 2016-06-06
- 権利情報
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- http://creativecommons.org/licenses/by/4.0/
- http://creativecommons.org/licenses/by/4.0/
- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.7554/elife.14023
- 公開者
- eLife Sciences Publications, Ltd
説明
<jats:p>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.</jats:p>
収録刊行物
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- eLife
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eLife 5 e14023-, 2016-06-06
eLife Sciences Publications, Ltd