NCoR1 fine‐tunes type‐I IFN response in cDC1 dendritic cells by directly regulating Myd88‐IRF7 axis under TLR9

Détails

ID Serval
serval:BIB_CEF35453005F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
NCoR1 fine‐tunes type‐I IFN response in cDC1 dendritic cells by directly regulating Myd88‐IRF7 axis under TLR9
Périodique
European Journal of Immunology
Auteur(s)
Ahad Abdul, Smita Shuchi, Mishra Gyan Prakash, Biswas Viplov Kumar, Sen Kaushik, Gupta Bhawna, Garcin Dominique, Acha-Orbea Hans, Raghav Sunil K.
ISSN
0014-2980
1521-4141
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
12/2020
Peer-reviewed
Oui
Volume
50
Numéro
12
Pages
1959-1975
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Plasmacytoid dendritic cells (DCs) are reported to induce robust type-I interferon (IFN) response, whereas cDC1 DCs develop moderate type-I IFN response upon TLR9 stimulation. It is very interesting to understand how this signaling under TLR9 is tightly regulated for the induction of type-I IFNs. Here, we report co-repressor protein NCoR1 as the major factor fine-tuning the signaling pathways regulating IFN-β expression under TLR9 in cDC1 DCs. We found that NCoR1 knockdown induced a robust IFN-β-mediated antiviral response upon TLR9 activation in cDC1 DCs. At the molecular level, we showed that NCoR1 directly repressed MyD88-IRF7 signaling axis in cDC1 cells. Therefore, NCoR1 depletion enhanced pIRF7 levels, IFN-β secretion, and downstream pSTAT1-pSTAT2 signaling, leading to sustained induction of IFN stimulatory genes. Integrative genomic analysis depicted strong enrichment of an antiviral gene-module in CpG-activated NCoR1 knockdown DCs upon TLR9 activation. Moreover, we confirmed our findings in primary DCs derived from splenocytes of WT and NCoR1 DC <sup>-/-</sup> animals, which showed protection from Sendai and Vesicular Stomatitis viruses upon CpG activation. Ultimately, we identified that NCoR1-HDAC3 complex is involved in repressing the type-I IFN response in cDC1 DCs.
Mots-clé
Immunology, Immunology and Allergy
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/07/2020 11:23
Dernière modification de la notice
08/07/2021 6:37
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