期刊
SCIENCE ADVANCES
卷 5, 期 11, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax3511
关键词
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资金
- Labex EpiGenMed, an Investissements d'avenir program [ANR-10-LABX-12-01]
- Agence National de la Recherche sur le SIDA et les Hepatites virales, ANRS [AO2017-1]
- European Community's Seventh Framework Program (FP7-PEOPLE-2011-ITN) under the Marie-Curie Initial Training Network FishForPharma [PITN-GA-2011-289209]
- European Community's H2020 Program Marie-Curie Innovative Training Network ImageInLife [721537]
- Agence Nationale de la Recherche [ANR-16-CE20-0002-03, ANR-10-MDI-009]
- Region Occitanie (REPERE2017ImageInLife)
- ANRS [AO2017-1, AO2018-2, AO2016-1, AO2017-2]
- program Investissement d'avenir TEFOR [ANR-II-INSB-0014]
- European Molecular Biology Organization EMBO [LT-834-2017]
- start-up funding program Baustein of the Medical Faculty of Ulm University [LSBN.0147]
- Deutsche Forschungsgemeinschaft DFG [SM 544/1-1]
- Marie Curie Actions (MSCA) [721537] Funding Source: Marie Curie Actions (MSCA)
Plasmacytoid dendritic cells (pDCs) play a crucial role in antiviral innate immunity through their unique capacity to produce large amounts of type I interferons (IFNs) upon viral detection. Tripartite motif (TRIM) proteins have recently come forth as important modulators of innate signaling, but their involvement in pDCs has not been investigated. Here, we performed a rationally streamlined small interfering RNA (siRNA)-based screen of TRIM proteins in human primary pDCs to identify those that are critical for the IFN response. Among candidate hits, TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function. Mechanistically, TRIM8 protects phosphorylated IRF7 (pIRF7) from proteasomal degradation in an E3 ubiquitin ligase-independent manner by preventing its recognition by the peptidyl-prolyl isomerase Pin1. Our findings uncover a previously unknown regulatory mechanism of type I IFN production in pDCs by which TRIM8 and Pin1 oppositely regulate the stability of pIRF7.
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