Notch signaling protects CD4 T cells from STING-mediated apoptosis during acute systemic inflammation.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
30
04
2020
accepted:
11
08
2020
entrez:
24
9
2020
pubmed:
25
9
2020
medline:
14
4
2022
Statut:
epublish
Résumé
Dysregulation of T cell apoptosis contributes to the pathogenesis of acute systemic inflammation-induced immunosuppression, as seen in sepsis and trauma. However, the regulatory mechanisms of T cell apoptosis are unclear. Activation of stimulator of interferon genes (STING) has been shown to induce T cell apoptosis. Notch was previously identified as the top negative regulator of STING in macrophages through a kinase inhibitor library screening. However, how Notch signaling regulates STING activation in T cells is unknown. Here, using a γ-secretase inhibitor to block Notch signaling, we found that Notch protected CD4 T cells from STING-mediated apoptosis during endotoxemia. Mechanistically, Notch intracellular domain (NICD) interacted with STING at the cyclic dinucleotide (CDN) binding domain and competed with CDN to inhibit STING activation. In conclusion, our data reveal a previously unidentified role of Notch in negative regulation of STING-mediated apoptosis in CD4 T cells.
Identifiants
pubmed: 32967837
pii: 6/39/eabc5447
doi: 10.1126/sciadv.abc5447
pmc: PMC7531880
pii:
doi:
Substances chimiques
Amyloid Precursor Protein Secretases
EC 3.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI152044
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM127027
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Références
Trends Immunol. 2015 Dec;36(12):802-814
pubmed: 26617322
Elife. 2016 May 24;5:
pubmed: 27218451
Dev Cell. 2005 Jun;8(6):867-79
pubmed: 15935776
Cell Death Dis. 2016 Dec 8;7(12):e2515
pubmed: 27929540
Blood. 2013 Apr 4;121(14):2638-46
pubmed: 23380742
Nat Immunol. 2004 Mar;5(3):247-53
pubmed: 14985712
Nat Rev Genet. 2019 Nov;20(11):657-674
pubmed: 31358977
Cell Death Dis. 2012 Aug 23;3:e380
pubmed: 22914328
Science. 2013 Feb 15;339(6121):826-30
pubmed: 23258412
Eur J Immunol. 2009 Sep;39(9):2556-70
pubmed: 19662631
Nat Immunol. 2020 Jan;21(1):17-29
pubmed: 31819255
Cancer Res. 2019 Feb 1;79(3):639-649
pubmed: 30563887
Adv Exp Med Biol. 2012;727:199-209
pubmed: 22399349
Sci Transl Med. 2019 May 29;11(494):
pubmed: 31142678
Cancer Immunol Res. 2014 Aug;2(8):800-11
pubmed: 24830414
Cancer Res. 2016 Apr 15;76(8):2137-52
pubmed: 26951929
J Immunol. 2011 Sep 1;187(5):2595-601
pubmed: 21813776
Nat Med. 2015 Jan;21(1):55-61
pubmed: 25501905
Immunol Lett. 2015 Nov;168(1):41-50
pubmed: 26362089
Int Immunopharmacol. 2019 Nov;76:105907
pubmed: 31525636
N Engl J Med. 2014 Aug 7;371(6):507-518
pubmed: 25029335
J Clin Invest. 2016 Jan;126(1):23-31
pubmed: 26727230
Nagoya J Med Sci. 2011 Feb;73(1-2):49-57
pubmed: 21614937
Nature. 2009 Oct 8;461(7265):788-92
pubmed: 19776740
Science. 2013 Feb 15;339(6121):786-91
pubmed: 23258413
Immunity. 2010 Jan 29;32(1):14-27
pubmed: 20152168
Nat Commun. 2017 Sep 5;8(1):427
pubmed: 28874664
World J Emerg Med. 2017;8(4):292-296
pubmed: 29123608
JAMA. 2011 Dec 21;306(23):2594-605
pubmed: 22187279
J Immunol. 2014 Feb 1;192(3):1162-70
pubmed: 24391220
BMC Dev Biol. 2001;1:13
pubmed: 11495630
Immunity. 2013 Jul 25;39(1):148-59
pubmed: 23890069
Nat Immunol. 2015 Nov;16(11):1162-73
pubmed: 26437242
Nucleic Acids Res. 2018 May 4;46(8):4054-4071
pubmed: 29547894
Sci Transl Med. 2017 Oct 18;9(412):
pubmed: 29046432
J Leukoc Biol. 2014 Nov;96(5):767-77
pubmed: 24791959
Mol Cell. 2015 Sep 17;59(6):891-903
pubmed: 26300263
Cell Signal. 2014 Nov;26(11):2299-305
pubmed: 25101857
Nature. 2011 Sep 25;478(7370):515-8
pubmed: 21947006
Nat Rev Immunol. 2006 Nov;6(11):813-22
pubmed: 17039247