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TRIM8 is required for virus-induced IFN response in human plasmacytoid dendritic cells
- Source :
- Science Advances, Science Advances, American Association for the Advancement of Science (AAAS), 2019, 5 (11), pp.eaax3511. ⟨10.1126/sciadv.aax3511⟩, Science Advances, 2019, 5 (11), pp.eaax3511. ⟨10.1126/sciadv.aax3511⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- TRIM8 and Pin1 oppositely control IRF7-induced interferon production.<br />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.
- Subjects :
- Small interfering RNA
Interferon Regulatory Factor-7
Ubiquitin-Protein Ligases
[SDV]Life Sciences [q-bio]
Immunology
Regulator
Nerve Tissue Proteins
Cell Line
03 medical and health sciences
0302 clinical medicine
Ubiquitin
Interferon
medicine
Animals
Humans
Phosphorylation
RNA, Small Interfering
Research Articles
Zebrafish
030304 developmental biology
0303 health sciences
Multidisciplinary
Innate immune system
biology
Influenza A Virus, H3N2 Subtype
SciAdv r-articles
hemic and immune systems
Dendritic Cells
Tripartite motif family
Immunity, Innate
3. Good health
Cell biology
NIMA-Interacting Peptidylprolyl Isomerase
HEK293 Cells
Interferon Type I
biology.protein
PIN1
HIV-1
IRF7
[SDV.IMM]Life Sciences [q-bio]/Immunology
RNA Interference
Carrier Proteins
Chikungunya virus
030215 immunology
medicine.drug
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 23752548
- Database :
- OpenAIRE
- Journal :
- Science Advances, Science Advances, American Association for the Advancement of Science (AAAS), 2019, 5 (11), pp.eaax3511. ⟨10.1126/sciadv.aax3511⟩, Science Advances, 2019, 5 (11), pp.eaax3511. ⟨10.1126/sciadv.aax3511⟩
- Accession number :
- edsair.doi.dedup.....7c12764eb916b52f5082cd4ed9ec0647