ArticleThe Journal of experimental medicine2008
PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 226 citations in OpenAlex.
- BST2/Tetherin is constitutively expressed on human thymocytes with the phenotype and function of Treg cells.European journal of immunology · 2015Trial
- IRF1 regulates apoptosis and osteogenic differentiation of bone marrow mesenchymal stem cells and ameliorates osteoporosis by activating the PI3K/AKT signaling pathway.Journal of advanced research · 2026Article
- The SLC15A4-LAMTOR1 interaction licenses endolysosomal TLR-mediated mTOR signaling and inflammatory cytokine production.bioRxiv : the preprint server for biology · 2026Article
- Article
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- Type III interferon primes pDCs for TLR7 activation and antagonizes immune suppression mediated by TGF-β and PGE2.Nature communications · 2025Article
- Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.The Journal of experimental medicine · 2025Article
- Resiquimod induces a mixed Th1 and Th2 response via STAT1 and STAT3 signalling in chickens.Biochemistry and biophysics reports · 2025Article
- Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study.Frontiers in immunology · 2024Article
- The crucial regulatory role of type I interferon in inflammatory diseases.Cell & bioscience · 2023Review
- Disruption of endosomal trafficking with EGA alters TLR9 cytokine response in human plasmacytoid dendritic cells.Frontiers in immunology · 2023Article
- IRF7: role and regulation in immunity and autoimmunity.Frontiers in immunology · 2023Review
- The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis.Nature communications · 2022Article
- Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19.Science immunology · 2022Article
- Class I PI3K regulatory subunits control differentiation of dendritic cell subsets and regulate Flt3L mediated signal transduction.Scientific reports · 2022Article
- Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation.The Journal of experimental medicine · 2022Article
- Article
- Class I PI3K Biology.Current topics in microbiology and immunology · 2022Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmacytoid predendritic cells (pDCs) are the main producers of type I interferon (IFN) in response to Toll-like receptor (TLR) stimulation. Phosphatidylinositol-3 kinase (PI3K) has been shown to be activated by TLR triggering in multiple cell types; however, its role in pDC function is not known. We show that PI3K is activated by TLR stimulation in primary human pDCs and demonstrate, using specific inhibitors, that PI3K is required for type I IFN production by pDCs, both at the transcriptional and protein levels. Importantly, PI3K was not involved in other proinflammatory responses of pDCs, including tumor necrosis factor alpha and interleukin 6 production and DC differentiation. pDCs preferentially expressed the PI3K delta subunit, which was specifically involved in the control of type I IFN production. Although uptake and endosomal trafficking of TLR ligands were not affected in the presence of PI3K inhibitors, there was a dramatic defect in the nuclear translocation of IFN regulatory factor (IRF) 7, whereas nuclear factor kappaB activation was preserved. Thus, PI3K selectively controls type I IFN production by regulating IRF-7 nuclear translocation in human pDCs and could serve as a novel target to inhibit pathogenic type I IFN in autoimmune diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.