ArticleThe Journal of biological chemistry2014
Interferon regulatory factor 6 differentially regulates Toll-like receptor 2-dependent chemokine gene expression in epithelial cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes.Nature communications · 2026Article
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- IRF6 C-terminal phosphorylation links inflammation and cell-cell adhesion in oral keratinocytes: implications for oral lichen planus.BMC immunology · 2025Article
- Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.American journal of human genetics · 2025Article
- IRF6 regulates adherens junction proteins and inflammatory cytokines in salivary acinar cells and its expression is elevated in Sjӧgren's syndrome.Archives of oral biology · 2025Article
- IRF6 Enhances IFN-β Expression and Inhibits Viral Replication to Reduce the Severity of Herpetic Stromal Keratitis.Journal of inflammation research · 2025Article
- A novel noncanonical function for IRF6 in the recycling of E-cadherin.Molecular biology of the cell · 2024Article
- HIV-Host Cell Interactions.Cells · 2023Review
- Targeting transcription factors for therapeutic benefit in rheumatoid arthritis.Frontiers in immunology · 2023Review
- Negative regulation of interferon regulatory factor 6 (IRF6) in interferon and NF-κB signalling pathways of common carp (Cyprinus carpio L.).BMC veterinary research · 2022Article
- Sublytic C5b-9 Induces CCL3/4 Production and Macrophage Accumulation in Thy-1N Rats via PKC-α/p65/IRF-8 Axis.International journal of biological sciences · 2022Article
- Targeted Transcriptomics of Frog Virus 3 in Infected Frog Tissues Reveal Non-Coding Regulatory Elements and microRNAs in the Ranaviral Genome and Their Potential Interaction with Host Immune Response.Frontiers in immunology · 2021Article
- TLR-4, TLR-5 and IRF4 are diagnostic markers of knee osteoarthritis in the middle-aged and elderly patients and related to disease activity and inflammatory factors.Experimental and therapeutic medicine · 2020Article
- Interferon regulatory factor 6 is required for proper wound healing in vivo.Developmental dynamics : an official publication of the American Association of Anatomists · 2020Article
- A cleft lip and palate gene, Irf6, is involved in osteoblast differentiation of craniofacial bone.Developmental dynamics : an official publication of the American Association of Anatomists · 2019Article
- Effect of IL-36γ expression on chronic periodontitis with an increase in NF-KB signaling pathway.Journal of advanced periodontology & implant dentistry · 2019Article
- Integrative Analysis IdentifiedFrontiers in neurology · 2019Article
- ErbB2-driven downregulation of the transcription factor Irf6 in breast epithelial cells is required for their 3D growth.Breast cancer research : BCR · 2018Article
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal and mucosal epithelial cells are integral to host defense. They not only act as a physical barrier but also utilize pattern recognition receptors, such as the Toll-like receptors (TLRs), to detect and respond to pathogens. Members of the interferon regulatory factor (IRF) family of transcription factors are key components of TLR signaling as they impart specificity to downstream responses. Although IRF6 is a critical regulator of epithelial cell proliferation and differentiation, its role in TLR signaling has not previously been addressed. We show here that IRF6 is activated by IRAK1 as well as by MyD88 but not by TRIF or TBK1. Co-immunoprecipitation experiments further demonstrated that IRF6 can interact with IRAK1. Gene silencing in epithelial cells along with gene promoter reporter assays showed that IRAK1 mediates TLR2-inducible CCL5 gene expression at least in part by promoting IRF6 activation. Conversely, IRAK1 regulated CXCL8 gene expression independently of IRF6, thus identifying a molecular mechanism by which TLR2 signaling differentially regulates the expression of specific chemokines in epithelial cells. Bioinformatics analysis and mutagenesis-based experiments identified Ser-413 and Ser-424 as key regulatory sites in IRF6. Phosphomimetic mutation of these residues resulted in greatly enhanced IRF6 dimerization and trans-activator function. Collectively, our findings suggest that, in addition to its importance for epithelial barrier function, IRF6 also contributes to host defense by providing specificity to the regulation of inflammatory chemokine expression by TLR2 in epithelial cells.
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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.