Affinage

IRF6

Interferon regulatory factor 6 · UniProt O14896

Length
467 aa
Mass
53.1 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF6 is a transcription factor central to epithelial differentiation, morphogenesis, and barrier formation, functioning as a key effector downstream of p63, Notch, and TGFβ/SMAD4 signaling pathways. It is phosphorylated by RIPK4 at Ser413 and Ser424 to activate its transactivation function, whereupon it drives expression of genes controlling lipid metabolism, tight junctions, periderm integrity, and cell cycle exit, while simultaneously promoting proteasome-mediated degradation of p63 to limit keratinocyte proliferative potential (PMID:31578523, PMID:21807998, PMID:25784454). Loss-of-function mutations cause Van der Woude syndrome and dominant-negative mutations cause popliteal pterygium syndrome, reflecting IRF6's essential role in orofacial and skin development (PMID:12219090). IRF6 also functions in innate immune signaling by regulating inflammatory cytokines including IL-36γ, CCL5, CXCL11, and IL-1β, and its epigenetic silencing by EMT transcription factors ZEB1/SNAIL in tumor cells confers resistance to TNF-α-mediated apoptosis during immunotherapy (PMID:26819203, PMID:27014863, PMID:38378697).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Identifying the causative gene for Van der Woude and popliteal pterygium syndromes established that a member of the IRF transcription factor family has a non-immune, developmental role in orofacial and skin morphogenesis.

    Evidence Mutation screening and in situ hybridization in affected families and mouse embryos

    PMID:12219090

    Open questions at the time
    • DNA-binding targets unknown
    • mechanism of action in epithelial differentiation uncharacterized
    • post-translational regulation unknown
  2. 2009 High

    Demonstrating that Irf6 knockout mice have defective oral periderm integrity and pathological epithelial adhesions defined the cellular basis of IRF6's role in palatogenesis — maintaining a specialized surface epithelium (periderm) that prevents inappropriate tissue fusion.

    Evidence Irf6 knockout mouse phenotyping, histology, and genetic interaction with Jagged2

    PMID:19439425

    Open questions at the time
    • Direct transcriptional targets mediating periderm formation not identified
    • relationship between IRF6 and Notch pathway only inferred from parallel phenotypes
  3. 2011 High

    Three studies converged to place IRF6 within interconnected signaling cascades: a Pbx–Wnt–p63–Irf6 module controlling midfacial morphogenesis, Notch signaling directly inducing IRF6 for keratinocyte differentiation and tumor suppression, and a reciprocal feedback loop in which p63 activates IRF6, which then triggers proteasomal p63 degradation to enforce cell cycle exit.

    Evidence Conditional knockout mice with ChIP and rescue (Pbx–Wnt); siRNA knockdown with in vivo differentiation and tumor assays (Notch); ChIP-seq, expression profiling, and invasion assays in SCC cells (p63 feedback)

    PMID:21807998 PMID:21909072 PMID:21982646

    Open questions at the time
    • Direct versus indirect Notch regulation of IRF6 promoter not fully resolved
    • genome-wide target overlap between Notch-driven and p63-driven IRF6 programs not compared
    • structural basis of IRF6–proteasome coupling to p63 degradation unknown
  4. 2013 High

    Genetic epistasis and rescue experiments placed IRF6 downstream of TGFβ/SMAD4 signaling in medial edge epithelium, establishing a third major input pathway and showing that IRF6 overexpression can compensate for loss of TGFβ receptor signaling during palatal fusion.

    Evidence Conditional Smad4 and Tgfbr2 knockout mice, Irf6 haploinsufficiency crosses, Irf6 overexpression rescue of p21 and MEE degeneration

    PMID:23406900

    Open questions at the time
    • Whether SMAD4 directly binds the IRF6 promoter or acts through p63 not distinguished
    • downstream target genes mediating MEE fate beyond p21 not identified
  5. 2014 High

    Characterization of a disease-associated MCS9.7 enhancer mutation revealed a dual mechanism — simultaneous loss of p63/E47 binding and gain of a Lef1/β-catenin repressor site — explaining how a single nucleotide change could profoundly silence IRF6 and refining understanding of IRF6 cis-regulation.

    Evidence Luciferase reporters in human cells, transgenic mouse lacZ assay, EMSA for p63, E47, and Lef1

    PMID:24442519

    Open questions at the time
    • Whether this dual mechanism operates at other IRF6 enhancers unknown
    • chromatin-level effects of the mutation not assessed
  6. 2014 High

    Demonstrating that RIPK4-deficient mice phenocopy IRF6 loss (periderm defects, epithelial fusions) and that kinase-dead RIPK4 fails to rescue IRF6-dependent gastrulation defects in Xenopus identified RIPK4 as the activating kinase for IRF6 and established kinase activity as essential.

    Evidence RIPK4 knockout mice, Xenopus dominant-negative IRF6 with wild-type or kinase-dead RIPK4 rescue

    PMID:25430793

    Open questions at the time
    • Precise phosphorylation sites not yet mapped in this study
    • direct kinase–substrate interaction not shown biochemically here
  7. 2015 High

    Mapping RIPK4 phosphorylation of IRF6 to Ser413 and Ser424 and showing that the VWS-associated R412X truncation causes proteasomal IRF6 degradation linked the biochemistry of RIPK4-IRF6 activation to specific disease mutations, explaining both VWS and BPS at the molecular level.

    Evidence Phospho-site mutagenesis, proteasome inhibition, reporter assays with disease-associated mutants

    PMID:25784454

    Open questions at the time
    • Crystal structure of phosphorylated IRF6 not available
    • whether additional kinases phosphorylate these sites in vivo unknown
  8. 2015 Medium

    Placing SNAI2 downstream of IRF6 in TGFβ3-mediated palatal fusion showed that IRF6 can promote epithelial-mesenchymal transition in a specific developmental context, complicating its general characterization as a differentiation/tumor suppressor factor.

    Evidence Palatal shelf organ culture with siRNA knockdown and IRF6 overexpression, EMT marker analysis

    PMID:26240017

    Open questions at the time
    • Whether IRF6 directly binds the SNAI2 promoter not demonstrated
    • relevance of this EMT-promoting activity outside palatal fusion not tested
  9. 2015 Medium

    Identifying IRF6 as a regulator of innate immune cytokines (IL-36γ via TLR2/IRAK1, and IL-23p19 via TLR3) in epithelial cells expanded IRF6's function beyond development into barrier immunity, revealing direct promoter regulation of inflammatory mediators.

    Evidence siRNA silencing, promoter reporter assays, TLR agonist stimulation in oral epithelial cells and keratinocytes

    PMID:26303210 PMID:26819203

    Open questions at the time
    • In vivo immune phenotype of Irf6-deficient epithelial barrier not assessed
    • genome-wide identification of IRF6 immune target genes not performed
  10. 2016 Medium

    Demonstrating that RIPK4 drives CCL5 and CXCL11 expression specifically through IRF6 transactivation unified the RIPK4-IRF6 kinase axis with inflammatory chemokine regulation, bridging the developmental and immune arms of IRF6 function.

    Evidence Overexpression and siRNA silencing of RIPK4 and IRF6, promoter reporter assays in keratinocytes

    PMID:27014863

    Open questions at the time
    • Whether RIPK4-IRF6 chemokine axis operates in vivo during infection or inflammation not tested
  11. 2016 High

    Tissue-specific Irf6 ablation in oral epithelium revealed that IRF6 maintains junctional integrity (restraining RHO GTPase activity), controls salivary gland morphogenesis, and sustains mucosal barrier defense against cariogenic bacteria, extending IRF6's epithelial functions to glandular homeostasis.

    Evidence Oral epithelium-specific Irf6 conditional knockout, RHO GTPase assay, saliva flow measurement, bacterial colonization assay

    PMID:27927890

    Open questions at the time
    • Direct transcriptional targets controlling RHO GTPase activity not identified
    • whether salivary phenotype is cell-autonomous not fully resolved
  12. 2018 High

    Showing that HPV16 E6 suppresses IRF6 transcription by degrading p53, which normally occupies the IRF6 promoter, identified p53 as a second transcription factor (alongside p63) directly activating IRF6, and revealed viral exploitation of this axis for immune evasion via IL-1β suppression.

    Evidence ChIP for p53 at IRF6 promoter in cervical cancer tissues, E6 mutants preventing p53 degradation, promoter reporters

    PMID:30089163

    Open questions at the time
    • Relative contributions of p53 versus p63 to IRF6 expression in normal keratinocytes not quantified
  13. 2019 High

    Multi-omic profiling of IRF6-deficient embryonic skin established that RIPK4 phosphorylation activates IRF6 at bivalent promoters to drive lipid metabolism and tight junction gene programs essential for epidermal barrier formation, providing a comprehensive mechanistic picture of the RIPK4-IRF6 differentiation axis.

    Evidence RNA-seq, ChIP-seq, and ATAC-seq of wild-type versus IRF6-deficient embryonic skin; phospho-site mutagenesis

    PMID:31578523

    Open questions at the time
    • Cofactors recruiting IRF6 to bivalent promoters not identified
    • whether IRF6 binding resolves bivalency or requires additional chromatin remodelers unknown
  14. 2024 High

    Discovery that EMT factors ZEB1 and SNAIL epigenetically silence IRF6 during acquired immunotherapy resistance in pancreatic cancer, rendering tumor cells resistant to TNF-α-mediated apoptosis, established a tumor cell-intrinsic immune evasion mechanism and expanded IRF6's tumor suppressor role to immunotherapy response.

    Evidence Mouse PDAC immunotherapy resistance model, RNA-seq, ChIP/epigenetic analysis, TNF-α killing assays

    PMID:38378697

    Open questions at the time
    • Direct IRF6 target genes mediating TNF-α sensitivity not identified
    • therapeutic potential of restoring IRF6 expression not tested
    • generalizability beyond pancreatic cancer unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of IRF6 activation upon RIPK4 phosphorylation, the identity of cofactors that recruit IRF6 to bivalent chromatin, and the full spectrum of direct genomic targets mediating its immune versus developmental functions remain to be determined.
  • No crystal or cryo-EM structure of IRF6 available
  • Genome-wide comparison of IRF6 targets in immune versus developmental contexts not performed
  • Whether IRF6 dimerizes with other IRF family members for specific functions is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3
Partners
IRAK1RIPK4SMAD4SPECC1LTP63TWIST1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 IRF6 encodes a transcription factor with a helix-turn-helix DNA-binding domain and a protein-binding domain; loss-of-function (haploinsufficiency) mutations cause Van der Woude syndrome and dominant-negative mutations cause popliteal pterygium syndrome, establishing IRF6 as required for orofacial and skin development. Expression analyses showed high Irf6 mRNA in medial edge epithelium of fusing palate, tooth buds, hair follicles, genitalia, and skin. Mutation identification by sequencing, expression analysis by in situ hybridization Nature genetics High 12219090
2011 A conserved Pbx-Wnt-p63-Irf6 regulatory module controls midfacial ectoderm development; Pbx proteins bind a midfacial regulatory element to drive Wnt9b-Wnt3 expression, which in turn regulates p63 and thereby Irf6, promoting epithelial apoptosis required for facial process fusion. Loss of Pbx in cephalic ectoderm suppresses midfacial apoptosis and causes cleft lip/palate, rescued by ectopic Wnt expression. Conditional knockout mice, ChIP, transgenic rescue experiments Developmental cell High 21982646
2011 IRF6 acts as a tumor suppressor in squamous cell carcinoma (SCC): it is transcriptionally activated by p63 and induces proteasome-mediated downregulation of p63, limiting keratinocyte proliferative potential. ChIP-seq and expression profiling identified direct IRF6 target genes regulating cell cycle, differentiation, adhesion, and cell-cell contact. IRF6 reintroduction into SCC cells strongly inhibits cell growth and invasiveness. ChIP-seq, siRNA knockdown, gene expression profiling, in vitro invasion assays, promoter methylation analysis Proceedings of the National Academy of Sciences of the United States of America High 21807998
2011 IRF6 is a primary Notch transcriptional target in keratinocytes; Notch activation induces IRF6 expression, and IRF6 is required for the pro-differentiation and tumor suppressive effects of Notch signaling. IRF6 downmodulation counteracts keratinocyte differentiation in vitro and in vivo and promotes ras-induced tumor formation. Reporter assays, siRNA knockdown, in vivo differentiation assays, tumor formation assays The EMBO journal High 21909072
2009 IRF6 and the Notch ligand Jagged2 function in convergent molecular pathways to control oral epithelial differentiation and periderm formation; IRF6 is essential for maintaining oral periderm integrity, spatiotemporal regulation of which determines appropriate palatal adhesion. Loss of Irf6 in mice leads to abnormal oral epithelial differentiation and pathological adhesion between palatal shelves and tongue. Mouse knockout analysis, tissue histology, in situ hybridization, genetic interaction studies Human molecular genetics High 19439425
2019 RIPK4 kinase phosphorylates IRF6 at Ser413 and Ser424, priming IRF6 for transcriptional activation. IRF6 and RIPK4 regulate overlapping biological processes in epidermal differentiation. IRF6 was enriched at bivalent promoters and its deficiency caused defective expression of genes involved in lipid metabolism and tight junction formation, resulting in abnormal stratum corneum lipid composition and severe epidermal barrier defect. RNA-seq, ChIP-seq, ATAC-seq of wild-type and IRF6-deficient mouse embryo skin, phosphorylation site mutagenesis Nature High 31578523
2014 RIPK4-deficient mice display epithelial fusions associated with abnormal periderm development and aberrant ectopic E-cadherin localization on the apical peridermal membrane. In Xenopus, IRF6 controls RIPK4 expression, and wild-type but not kinase-dead RIPK4 rescues gastrulation defects caused by dominant-negative IRF6. RIPK4 plays a role in cortical actin cytoskeleton organization in mouse epidermis and human HaCaT epithelial cells. Mouse and Xenopus knockdown/overexpression, rescue experiments with kinase-dead RIPK4, immunofluorescence for E-cadherin and actin Cell death and differentiation High 25430793
2013 TGFβ signaling via SMAD4 regulates IRF6 expression and MEE fate during palatal fusion. Haploinsufficiency of Irf6 in mice with Smad4 deletion in basal epithelium results in MEE persistence; overexpression of Irf6 rescues p21 expression and MEE degeneration in Tgfbr2-deficient mice, placing IRF6 downstream of TGFβ/SMAD4 in palatal fusion. Conditional knockout mice, genetic epistasis, in vivo Irf6 overexpression rescue experiments, p21 expression analysis Development (Cambridge, England) High 23406900
2015 IRF6 phosphorylation by RIPK4 at Ser413 and Ser424 induces IRF6 transactivation function; the VWS-associated p.Arg412X truncation causes rapid proteasome-dependent IRF6 degradation and prevents RIPK4-induced transactivation. The BPS-associated RIPK4 p.Ser376X mutation impairs RIPK4 induction of IRF6 transactivator function and also inhibits RIPK4-mediated β-catenin stabilization. Transfection with mutant constructs, proteasome inhibition assay, reporter assays for transactivation, co-expression experiments Cellular signalling High 25784454
2015 TGFβ3 increases IRF6 expression, which subsequently upregulates SNAI2 (an EMT regulator) and downregulates epithelial markers (E-cadherin, Plakophilin, ZO-1), promoting epithelial-mesenchymal transition during palatal fusion. Blocking SNAI2 delays palatal fusion and abolishes the IRF6 rescue effect, placing SNAI2 downstream of IRF6 in TGFβ3-mediated palatogenesis. Palatal shelf organ culture, siRNA knockdown, ectopic IRF6 overexpression, immunofluorescence for EMT markers Scientific reports Medium 26240017
2015 IRF6 acts downstream of IRAK1 (IL-1R-associated kinase 1) in TLR2 signaling to stimulate IL-36γ expression in human oral epithelial cells in response to Porphyromonas gingivalis. Gene silencing and promoter assays demonstrated IRF6 directly regulates IL-36γ promoter activity. siRNA gene silencing, gene promoter reporter assays, TLR2 agonist stimulation Journal of immunology Medium 26819203
2015 IRF6 regulates TLR3-dependent IL-23p19 expression in human keratinocytes; IRF6 silencing enhances poly(IC)-inducible IFN-β and inhibits IL-23p19 expression. Overexpression of IRF6 increases IL-23p19 promoter activity but inhibits IFN-β promoter activity. IL-23p19 and EBI3 interact (forming a novel heterodimer) as shown by co-immunoprecipitation and proximity ligation assays. siRNA silencing, reporter assays, co-immunoprecipitation, proximity ligation assay Immunology and cell biology Medium 26303210
2016 RIPK4 and IRF6 function as a signaling axis in keratinocytes to regulate proinflammatory cytokine expression; RIPK4 overexpression specifically induces CCL5 and CXCL11 through IRF6-mediated transactivation of their promoters. Gene silencing confirmed that inducible CCL5 and CXCL11 expression requires both RIPK4 and IRF6. Overexpression, siRNA silencing, gene reporter assays Cytokine Medium 27014863
2014 A mutation (350dupA) in the conserved IRF6 enhancer element MCS9.7 abrogates p63 and E47 binding to overlapping cis-motifs and disrupts enhancer activity; additionally, the mutation creates a CAAAGT Lef1 binding site that enables Lef1/β-Catenin to repress MCS9.7 enhancer activity, demonstrating a dual loss- and gain-of-function mechanism at the IRF6 regulatory element. Luciferase reporter assays in human cell cultures, transgenic mouse lacZ reporter assay, EMSA/binding assays for p63, E47, and Lef1 Human molecular genetics High 24442519
2018 HPV16 E6 oncoprotein inhibits IRF6 transcription by degrading p53, which normally binds the IRF6 promoter to drive its expression. IRF6 in turn regulates IL-1β promoter activity in human keratinocytes. HPV16 thus exploits p53 degradation to suppress IRF6 and block IL-1β production as an immune evasion mechanism. siRNA against E6, E6 point mutants preventing p53 degradation, ChIP for p53 at IRF6 promoter in cervical cancer tissues, IRF6 promoter reporter assays PLoS pathogens High 30089163
2019 Over-expression of Irf6 in mice causes exencephaly by suppressing Tfap2a and Grhl3 expression; conversely, loss of Irf6 reduces Tfap2a and Grhl3 in tail tissues and causes a curly tail phenotype, establishing Irf6 within a Tfap2a-Irf6-Grhl3 genetic pathway conserved in both orofacial and neural tube morphogenesis. Irf6 overexpression and loss-of-function mouse models, expression analysis of Tfap2a and Grhl3, human spina bifida sequencing Human molecular genetics Medium 30689861
2017 Loss of Irf6 causes craniosynostosis and mandibular hypoplasia; Irf6 and Twist1 interact genetically (double heterozygotes have severe mandibular hypoplasia/agnathia), with reduced EDN1 and downstream DLX5, DLX6, HAND2 expression in mesenchymal cells. Exogenous EDN1 peptides partially rescue Meckel's cartilage abnormalities, and partial rescue also occurs with p53 haploinsufficiency. Double heterozygous mouse crosses, spatiotemporal expression analysis, mandibular explant treatment with EDN1, p53 genetic rescue Scientific reports Medium 28769044
2024 EMT transcription factors ZEB1 and SNAIL epigenetically and transcriptionally silence IRF6 during acquired resistance to immunotherapy in pancreatic ductal adenocarcinoma. IRF6 silencing renders tumor cells less sensitive to TNF-α-mediated pro-apoptotic effects, establishing a tumor cell-intrinsic mechanism of resistance distinct from immune evasion. Mouse PDAC immunotherapy resistance model, RNA-seq, ChIP/epigenetic analysis, functional TNF-α killing assays Nature communications High 38378697
2012 Irf6 mutant mice show evagination (rather than invagination) of incisor epithelium similar to Ikkα mutants, with upregulation of canonical Wnt signaling in evaginated incisor epithelium; IRF6 regulates epithelial invagination in an NF-κB-independent manner. Irf6 mouse mutant analysis, in situ hybridization, immunohistochemistry for Wnt pathway components and NF-κB Developmental biology Medium 22366192
2020 SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves, and SPECC1L deficiency causes periderm layer abnormalities similar to Irf6 hypomorphic mutants, placing SPECC1L downstream of IRF6 in palatogenesis. SPECC1L mutations that disrupt microtubule association are linked to syndromic CL/P. Irf6 mutant mouse expression analysis, conditional Specc1l knockout mouse, epistasis by genetic cross, immunofluorescence Human molecular genetics Medium 31943082
2008 IRF6 was identified as a binding partner of maspin in mammary epithelial cells; IRF6 functions synergistically with maspin to regulate mammary epithelial cell differentiation by acting on the cell cycle, promoting exit from the cell cycle and entry into G0 quiescence. Protein interaction studies, cell cycle analysis Cell cycle (Georgetown, Tex.) Low 18604160
2016 Conditional ablation of Irf6 in late embryonic oral epithelium results in dysplastic salivary glands with disrupted epithelial junctional complexes (associated with elevated RHO GTPase activation), increased salivary cell proliferation, reduced saliva flow and buffering capacity, decreased CCL27 expression, and increased colonization by cariogenic bacteria. Conditional Irf6 knockout mouse (oral epithelium-specific), histology, RHO GTPase activity assay, saliva flow measurement, bacterial colonization assay Journal of dental research High 27927890
2017 Human IRF6 missense variant protein function can be assessed by ability to rescue the irf6-/- periderm rupture phenotype in zebrafish via mRNA microinjection; many variants predicted computationally to be loss-of-function retained partial or full protein function, enabling grouping into wild-type function, reduced function, and complete loss-of-function categories. Zebrafish irf6-/- rescue with human IRF6 variant mRNA microinjection, mRNA dosage titration PLoS genetics Medium 28945736
2020 Lin28A stabilizes lncRNA SNHG14, which promotes IRF6 mRNA degradation by targeting its 3' UTR via STAU1-mediated mRNA decay; this reduces IRF6 expression and consequently relieves IRF6-mediated transcriptional repression of PKM2 and GLUT1, thereby promoting aerobic glycolysis in glioma cells. RNA stability assays, siRNA knockdown, mRNA interaction assays, xenograft tumor models, ChIP/promoter assays for PKM2 and GLUT1 Cell death & disease Medium 32527996
2015 IRF6 is involved in cell proliferation and transformation in MCF10A breast epithelial cells downstream of Notch signaling; ΔNp63 downregulation by Notch contributes to IRF6 expression, and IRF6 abrogation impairs Notch-induced proliferation and transformation, demonstrating a context-dependent role for IRF6 as a positive regulator of proliferation downstream of Notch in these cells. siRNA knockdown, Notch activation, proliferation and transformation assays PloS one Medium 26161746

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nature genetics 652 12219090
1994 Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. The Journal of experimental medicine 622 7505800
2019 Innate immunity to intracellular LPS. Nature immunology 478 30962589
2019 Pushing the envelope: LPS modifications and their consequences. Nature reviews. Microbiology 381 31142822
2016 Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer. Immunity 339 27986454
1998 LPS-binding proteins and receptors. Journal of leukocyte biology 339 9665271
1997 T cell stimulation in vivo by lipopolysaccharide (LPS). The Journal of experimental medicine 260 9182680
2007 Structural biology of the LPS recognition. International journal of medical microbiology : IJMM 215 17481951
1992 Control of lipopolysaccharide (LPS) binding and LPS-induced tumor necrosis factor secretion in human peripheral blood monocytes. Journal of immunology (Baltimore, Md. : 1950) 207 1375247
2016 Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthritis and cartilage 204 27216281
2020 Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation. Neurobiology of disease 188 32087283
2019 ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway. Experimental and molecular pathology 172 31805278
2011 A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Developmental cell 160 21982646
2001 Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins. The Journal of clinical investigation 160 11489942
1996 Catalytic properties of lipopolysaccharide (LPS) binding protein. Transfer of LPS to soluble CD14. The Journal of biological chemistry 155 8626747
2003 Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons. Journal of immunology (Baltimore, Md. : 1950) 154 12538700
2006 LPS-induced TNF-alpha factor (LITAF)-deficient mice express reduced LPS-induced cytokine: Evidence for LITAF-dependent LPS signaling pathways. Proceedings of the National Academy of Sciences of the United States of America 153 16954198
2011 Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas. Proceedings of the National Academy of Sciences of the United States of America 141 21807998
2017 Corylin protects LPS-induced sepsis and attenuates LPS-induced inflammatory response. Scientific reports 125 28397806
2008 Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 125 19109745
1993 Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein. Journal of immunology (Baltimore, Md. : 1950) 125 7681085
2009 Integration of IRF6 and Jagged2 signalling is essential for controlling palatal adhesion and fusion competence. Human molecular genetics 116 19439425
1999 A growing family of receptor genes for lysophosphatidic acid (LPA) and other lysophospholipids (LPs). Cell biochemistry and biophysics 116 10356643
2016 Micheliolide inhibits LPS-induced inflammatory response and protects mice from LPS challenge. Scientific reports 105 26984741
2011 IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes. The EMBO journal 101 21909072
2011 Lactoferrin-lipopolysaccharide (LPS) binding as key to antibacterial and antiendotoxic effects. International immunopharmacology 100 22101278
1994 Hemoglobin, a newly recognized lipopolysaccharide (LPS)-binding protein that enhances LPS biological activity. The Journal of biological chemistry 99 7929195
2005 Variation in IRF6 contributes to nonsyndromic cleft lip and palate. American journal of medical genetics. Part A 95 16096995
1997 Lipopolysaccharide (LPS)-binding proteins BPI and LBP form different types of complexes with LPS. The Journal of biological chemistry 95 9228038
2019 Regulated Assembly of LPS, Its Structural Alterations and Cellular Response to LPS Defects. International journal of molecular sciences 94 30654491
2014 Lipopolysaccharide (LPS) induces the apoptosis and inhibits osteoblast differentiation through JNK pathway in MC3T3-E1 cells. Inflammation 94 24272171
2007 Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations. Genetics in medicine : official journal of the American College of Medical Genetics 92 17438386
2015 Salidroside attenuates lipopolysaccharide (LPS) induced serum cytokines and depressive-like behavior in mice. Neuroscience letters 84 26300543
2000 LPS and cytokine-activated endothelium. Seminars in thrombosis and hemostasis 81 11129414
2007 Interferon regulatory factor 6 (IRF6) and fibroblast growth factor receptor 1 (FGFR1) contribute to human tooth agenesis. American journal of medical genetics. Part A 80 17318851
2013 Smad4-Irf6 genetic interaction and TGFβ-mediated IRF6 signaling cascade are crucial for palatal fusion in mice. Development (Cambridge, England) 76 23406900
2019 The RIPK4-IRF6 signalling axis safeguards epidermal differentiation and barrier function. Nature 73 31578523
2014 Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation. Laboratory investigation; a journal of technical methods and pathology 72 24566933
2000 Induction of proliferation and cytokine production in human T lymphocytes by lipopolysaccharide (LPS). Toxicology 69 11090938
1995 Lipopolysaccharide (LPS) neutralizing peptides reveal a lipid A binding site of LPS binding protein. The Journal of biological chemistry 69 7543094
2017 Optimized Triton X-114 assisted lipopolysaccharide (LPS) removal method reveals the immunomodulatory effect of food proteins. PloS one 66 28355240
2020 Lin28A promotes IRF6-regulated aerobic glycolysis in glioma cells by stabilizing SNHG14. Cell death & disease 59 32527996
2020 Border Control: Regulating LPS Biogenesis. Trends in microbiology 58 33036869
2014 Differential and opposing effects of imatinib on LPS- and ventilator-induced lung injury. American journal of physiology. Lung cellular and molecular physiology 57 25480336
2014 An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects. Human molecular genetics 55 24442519
2011 Lipopolysaccharide (LPS) inner-core phosphates are required for complete LPS synthesis and transport to the outer membrane in Pseudomonas aeruginosa PAO1. mBio 54 21810964
2009 New insight in LPS antagonist. Mini reviews in medicinal chemistry 52 19275723
2015 Cell rejuvenation and social behaviors promoted by LPS exchange in myxobacteria. Proceedings of the National Academy of Sciences of the United States of America 51 26038568
2015 TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes. Immunology and cell biology 50 26303210
2012 Hepatic uptake and deacylation of the LPS in bloodborne LPS-lipoprotein complexes. Innate immunity 49 22441700
2016 IRF6 Regulates the Expression of IL-36γ by Human Oral Epithelial Cells in Response to Porphyromonas gingivalis. Journal of immunology (Baltimore, Md. : 1950) 48 26819203
2009 Association between IRF6 SNPs and oral clefts in West China. Journal of dental research 47 19734457
2015 IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion. Scientific reports 46 26240017
2022 Pinostrobin ameliorates lipopolysaccharide (LPS)-induced inflammation and endotoxemia by inhibiting LPS binding to the TLR4/MD2 complex. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 43 36270256
2012 Interaction between IRF6 and TGFA genes contribute to the risk of nonsyndromic cleft lip/palate. PloS one 43 23029012
2012 Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation. Journal of neuroimmunology 43 23084372
2017 Gelsolin Inhibits the Inflammatory Process Induced by LPS. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 42 28135711
2014 A novel RIPK4-IRF6 connection is required to prevent epithelial fusions characteristic for popliteal pterygium syndromes. Cell death and differentiation 41 25430793
2011 MCS9.7 enhancer activity is highly, but not completely, associated with expression of Irf6 and p63. Developmental dynamics : an official publication of the American Association of Anatomists 38 22113860
2008 IRF6 in development and disease: a mediator of quiescence and differentiation. Cell cycle (Georgetown, Tex.) 38 18604160
2011 HDAC6 regulates LPS-tolerance in astrocytes. PloS one 37 22022450
2002 TLR4 and LPS hyporesponsiveness in humans. International journal of hygiene and environmental health 37 12040919
2014 Pretreatment of lipopolysaccharide (LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway. International journal of clinical and experimental pathology 34 25400741
2019 Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro. Antioxidants (Basel, Switzerland) 33 31906130
2018 Human papillomavirus type 16 antagonizes IRF6 regulation of IL-1β. PLoS pathogens 33 30089163
2015 Lack of LCAT reduces the LPS-neutralizing capacity of HDL and enhances LPS-induced inflammation in mice. Biochimica et biophysica acta 33 26170061
2017 Micheliolide suppresses LPS-induced neuroinflammatory responses. PloS one 32 29040306
2021 Dulaglutide Alleviates LPS-Induced Injury in Cardiomyocytes. ACS omega 31 33817486
2019 The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation. Human molecular genetics 31 30689861
2017 Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation. Pharmacological research 31 28288940
2014 LPS quantitation procedures. Methods in molecular biology (Clifton, N.J.) 31 24818921
2013 Granulocyte colony stimulating factor induces lipopolysaccharide (LPS) sensitization via upregulation of LPS binding protein in rat. PloS one 31 23437199
2017 Myricetin protects cardiomyocytes from LPS-induced injury. Herz 30 28357449
2017 Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial Development. Scientific reports 30 28769044
2003 Novel mutations in the IRF6 gene for Van der Woude syndrome. Human genetics 30 12920575
2017 Rapid functional analysis of computationally complex rare human IRF6 gene variants using a novel zebrafish model. PLoS genetics 29 28945736
1995 Prolonged expression of lipopolysaccharide (LPS)-induced inflammatory genes in whole blood requires continual exposure to LPS. Infection and immunity 29 7890395
2012 LPS-binding protein enables intestinal epithelial restitution despite LPS exposure. Journal of pediatric gastroenterology and nutrition 27 22002480
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