Affinage

IRF5

Interferon regulatory factor 5 · UniProt Q13568

Length
498 aa
Mass
56.0 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF5 is a signal-dependent transcription factor that converts innate immune receptor engagement into proinflammatory gene programs, acting downstream of the TLR-MyD88 pathway through physical association with MyD88 and TRAF6 to drive nuclear translocation and induction of IL-6, IL-12, and TNF-α, with Irf5-deficient mice failing to mount these responses and resisting endotoxin shock (PMID:15665823). Its activity is gated by a defined activation cascade: IRAK4 acts upstream through TAK1→IKKβ, which phosphorylates IRF5 at Ser445 and Ser462 to trigger dimerization and nuclear entry (PMID:25326420, PMID:25326418, PMID:28924041), with PYK2 also required for endogenous IRF5 activation in macrophages (PMID:34795257); the protein carries a constitutive-activation domain, an autoinhibitory domain, dual nuclear localization signals, and a CRM1-dependent nuclear export signal that together govern its shuttling (PMID:12138184, PMID:15556946). In the nucleus IRF5 binds ISRE and composite PU.1:ISRE motifs—cooperating physically with RelA/NF-κB p65—to activate IL-12/IL-23 family genes while repressing IL-10, thereby programming M1 macrophage polarization (PMID:21240265, PMID:25159141), and a specificity-determining residue excludes IRF5 homodimers from the IFN-promoter ISRE variants bound by IRF3/IRF7 (PMID:29361124). Beyond myeloid cells, IRF5 directly drives plasma cell commitment via the Prdm1/Blimp-1 promoter and B-cell class switching, supports Th1/Th17 differentiation and TCR signaling in CD4+ T cells, and mediates Fas/TRAIL death-receptor apoptosis upstream of caspase-8 (PMID:20176957, PMID:22535200, PMID:18268344, PMID:19028697, PMID:32610123). Endolysosomal TLR7/8/9 signaling to IRF5 is routed through the adaptor TASL, which binds SLC15A4 and recruits IRF5 via a pLxIS motif (PMID:32433612). IRF5 output is restrained by multiple negative regulators, including IKKα (which blocks the K63-ubiquitination required for activity), Lyn kinase, KAP1/TRIM28, and the CLEC2D–TLR2 axis that degrades MyD88 (PMID:19786094, PMID:27521268, PMID:22995936, PMID:37872182). Through these activities IRF5 is a central driver of inflammatory disease, with risk-associated promoter and looping variants increasing IRF5 expression and M1 polarization (PMID:36869052).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2002 High

    Established IRF5 as a DNA-damage-responsive transcription factor and defined the domain architecture and phosphosites needed for its transactivation, framing it as an inducible, phosphorylation-gated regulator before its innate-immune role was known.

    Evidence EMSA/reporter assays placing IRF5 as a direct p53 target, plus deletion and site-directed mutagenesis mapping activation/autoinhibitory domains and Ser477/Ser480

    PMID:11973653 PMID:12138184

    Open questions at the time
    • The physiological upstream kinase for Ser477/480 was not identified
    • Connection between p53-induced IRF5 and innate immune signaling not addressed
  2. 2004 High

    Resolved how IRF5 subcellular distribution is controlled, showing a CRM1-dependent nuclear export signal restrains it and that TBK1/IKKε phosphorylation, unlike for IRF3, does not activate it.

    Evidence Leptomycin B treatment, NES mutagenesis with subcellular imaging, and co-transfection kinase assays

    PMID:15556946

    Open questions at the time
    • Did not identify the activating kinase
    • Mechanism by which most IRF5 is held cytoplasmic in resting cells not fully defined
  3. 2005 High

    Identified the core innate-immune function of IRF5 as a MyD88/TRAF6-coupled transcription factor essential for TLR-induced proinflammatory cytokine production in vivo.

    Evidence Irf5-/- mouse genetics, co-IP of IRF5 with MyD88/TRAF6, nuclear translocation and cytokine assays, endotoxin shock challenge

    PMID:15665823

    Open questions at the time
    • Did not define the activating phosphorylation event downstream of MyD88/TRAF6
    • DNA-binding site preference at endogenous promoters not yet mapped
  4. 2006 Medium

    Clarified that IRF5 is not directly virus-activated like IRF3 and that constitutively active IRF5 drives FADD-independent apoptosis, distinguishing IRF5 from other IRFs functionally.

    Evidence Phosphorylation/dimerization/nuclear-translocation/DNA-binding assays and apoptosis assays with Bcl-xL and dominant-negative FADD

    PMID:16751392

    Open questions at the time
    • Endogenous activating stimuli not defined in this study
    • Apoptotic effector mechanism downstream of IRF5 not resolved
  5. 2009 Medium

    Began dissecting the modifications gating IRF5 activity, showing IKKα phosphorylation induces dimerization but inhibits activity by blocking the K63-ubiquitination IRF5 requires.

    Evidence Co-IP, in vitro kinase and ubiquitination assays, reporter assays

    PMID:19786094

    Open questions at the time
    • E3 ligase mediating K63 ubiquitination not identified
    • Limited independent replication of the IKKα inhibitory role
  6. 2010 Medium

    Showed IRF5 transactivation is coupled to chromatin-modifying complexes, with HDAC- and HAT-containing assemblies dynamically converting an IRF5 silencing complex to an activating one at target promoters.

    Evidence Co-IP with HDAC1/Sin3a/HATs, TSA inhibitor treatment, reporter assays, domain mapping

    PMID:20935208

    Open questions at the time
    • Promoter-specific recruitment of each complex not fully defined
    • Single-lab data without genome-wide validation
  7. 2011 High

    Defined IRF5 as the molecular driver of M1 macrophage polarization by directly activating IL-12/IL-23 family genes and repressing IL-10.

    Evidence ChIP at target promoters, IRF5 overexpression, expression profiling, polarization assays

    PMID:21240265

    Open questions at the time
    • Mechanism of IL-10 repression not detailed
    • Cofactor requirements at activating versus repressing targets not resolved
  8. 2012 Medium

    Extended IRF5's transcriptional roles into B-cell biology (class switching via repressing IRF8-driven Ikaros) and identified KAP1/TRIM28 and SETDB1 as corepressors of IRF5.

    Evidence Irf5-/- mice with SCID reconstitution and ChIP at ikzf1; AP-MS and functional knockdown for KAP1/TRIM28

    PMID:22535200 PMID:22995936

    Open questions at the time
    • KAP1/SETDB1-mediated repression mechanism at endogenous IRF5 targets not fully resolved
    • How IRF5 switches between activating and IRF8-antagonizing modes unclear
  9. 2014 High

    Identified the principal activating kinase axis as IKKβ phosphorylating IRF5 at Ser445 and Ser462 downstream of TAK1, the events required for dimerization, nuclear translocation, and cytokine/IFNβ output.

    Evidence In vitro kinase assays with recombinant IKKβ, MS phosphosite mapping, phospho-specific antibodies, Ser-to-Ala mutants, siRNA and pharmacological inhibition of IKKβ/TAK1

    PMID:25326418 PMID:25326420

    Open questions at the time
    • E3 ligase for the required K63 ubiquitination still unidentified
    • Whether both serines are phosphorylated simultaneously or sequentially not resolved
  10. 2014 High

    Mapped IRF5's genomic engagement and a key DNA-binding cofactor, showing it uses composite PU.1:ISRE motifs and physically partners with RelA to control a subset of inflammatory genes.

    Evidence Genome-wide ChIP-seq, protein:DNA microarrays, reciprocal co-IP, transcriptomics in IRF5- and RelA-deficient macrophages

    PMID:25159141

    Open questions at the time
    • Generality of the RelA dependency across cell types not established
    • Determinants selecting composite versus ISRE-only sites not defined
  11. 2014 High

    Broadened IRF5's direct-target repertoire to neuronal/glial contexts, defining an IRF8→IRF5→P2X4R axis driving neuropathic pain.

    Evidence ChIP at the P2rx4 promoter, Irf5-/- mice, behavioral pain assays, IRF8/IRF5 expression analysis

    PMID:24818655

    Open questions at the time
    • Signal triggering microglial IRF5 activation in vivo not pinpointed
    • Whether IRF8 regulates IRF5 directly at the transcriptional level not shown
  12. 2013 High

    Placed IRF5 within the cytosolic RNA-sensing pathway, showing IRF3/IRF5/IRF7 collectively are required for MAVS-dependent type I IFN/ISG responses in myeloid DCs.

    Evidence Irf3xIrf5xIrf7 triple-KO mouse genetics, microarray transcriptomics, viral infection and pathogenesis assays

    PMID:23300459

    Open questions at the time
    • The unique non-redundant IRF5 contribution versus IRF3/IRF7 not isolated
    • Direct MAVS-to-IRF5 biochemical link not demonstrated
  13. 2015 Medium

    Established additional negative-target and disease links, with IRF5 directly repressing TGFβ1 in adipose macrophages affecting metabolic disease, and ESR1-mediated transcriptional control of IRF5 underlying sex-biased IFN-α responses.

    Evidence Genome-wide expression analysis in Irf5-/- mice on high-fat diet; recombinant IRF5 delivery into human pDCs plus conditional Esr1 KO

    PMID:25939064 PMID:26519527

    Open questions at the time
    • Direct ChIP at TGFB1 not explicitly demonstrated
    • Mechanism of ESR1-driven IRF5 transcription not detailed
  14. 2016 High

    Identified key negative regulators and an additional receptor input, showing Lyn kinase suppresses IRF5 K63-ubiquitination/phosphorylation kinase-independently, and that NOD2 engages IRF5 with RIP2/IRAK1/TRAF6 to drive Akt2-dependent glycolysis and M1 polarization.

    Evidence Co-IP, ubiquitination assays, kinase-dead Lyn mutant, Lyn-/-Irf5+/- compound mice; co-IP of IRF5 signaling complex with Akt2 assays and human macrophage genotyping

    PMID:27521268 PMID:27545875

    Open questions at the time
    • How Lyn physically blocks ubiquitination mechanistically not resolved
    • Direct versus indirect IRF5–Akt2 connection not fully defined
  15. 2017 High

    Placed IRAK4 kinase activity at the apex of the MyD88→TAK1→IKKβ→IRF5 cascade, separable from NF-κB, validating IRF5 activation as a targetable inflammatory node.

    Evidence Selective IRAK4 inhibition in human monocytes with ChIP of IRF5 at cytokine promoters and transcriptomics

    PMID:28924041

    Open questions at the time
    • Whether IRAK4 phosphorylates IRF5 directly or only via the cascade not distinguished here
    • Selectivity of downstream gene effects not exhaustively mapped
  16. 2018 High

    Explained the molecular basis for IRF5's distinct promoter selectivity, identifying a specificity-determining residue that excludes IRF5 homodimers from the IFN-gene ISRE variants bound by IRF3/IRF7.

    Evidence Protein-binding microarrays of IRF5 homodimers, site-directed mutagenesis, reporter assays

    PMID:29361124

    Open questions at the time
    • In vivo consequences of the specificity residue not tested
    • How heterodimerization or cofactors alter this specificity not addressed
  17. 2019 High

    Demonstrated context-specific direct targets and a reciprocal IRF5/IRF4 polarization switch, with IRF5 binding M1 chemokine/cytokine promoters in intestinal disease and mutually antagonizing IRF4 in microglia.

    Evidence ChIP at Ccl4/Ccl5/Tnf/Il12b with myeloid-specific Irf5 KO NEC model; siRNA/overexpression/cKO with stroke model for the IRF5/IRF4 axis

    PMID:31086271 PMID:31892541

    Open questions at the time
    • Molecular basis of mutual IRF5/IRF4 suppression not fully defined
    • Upstream cues setting the IRF5:IRF4 balance unclear
  18. 2020 High

    Identified TASL/SLC15A4 as the missing adaptor linking endolysosomal TLR7/8/9 specifically to IRF5, and extended IRF5's roles into monocyte-to-macrophage differentiation, CD4+ T-cell TCR signaling/Th1-Th17 programs, and human antiviral immunity.

    Evidence TASL/SLC15A4 deletion and pLxIS-motif mutagenesis in human immune cells; Irf5-/- and conditional KO mice with scRNA-seq, colitis and infection models, human iPSC-DCs

    PMID:32075938 PMID:32433612 PMID:32444476 PMID:32610123

    Open questions at the time
    • Structural basis of TASL pLxIS recruitment of IRF5 not resolved
    • How a single factor coordinates such distinct cell-type programs unclear
  19. 2021 High

    Identified additional activating kinases and signal-convergence mechanisms, showing PYK2 is required for endogenous IRF5 activation, IRAK4 forms a MyD88/IRF5/IRF4 Myddosome in microglia, and BCR plus TLR7 synergize to raise IRF5 phosphorylation/expression to a lupus-relevant threshold in B cells.

    Evidence Kinase inhibitor screen and PYK2-deficient macrophages with defactinib; Myddosome co-IP and IRAK4 inhibition in microglia; B-cell-conditional Irf5 KO across lupus models

    PMID:33573200 PMID:34197340 PMID:34795257

    Open questions at the time
    • PYK2 phosphosite on IRF5 not mapped
    • How BCR and TLR7 inputs are integrated quantitatively to set the IRF5 threshold not resolved
  20. 2020 Medium

    Established IRF5 dimerization as a druggable step, with cell-penetrating peptides that bind IRF5 and block homodimerization acting downstream of phosphorylation to reduce nuclear pSer462-IRF5 and IFN-α.

    Evidence Biochemical binding, live-cell imaging, dimerization and IFN-α assays, flow cytometry of nuclear pIRF5 in pDCs

    PMID:32440537

    Open questions at the time
    • In vivo efficacy and selectivity not established
    • Structural detail of the disrupted dimer interface not resolved
  21. 2023 High

    Connected human autoimmune-risk genetics to IRF5 dosage and showed inhibitory checkpoints, with the rs4728142/ZBTB3 looping mechanism raising IRF5-short transcript and M1 polarization, and CLEC2D-TLR2 degrading MyD88 to limit IRF5 activation.

    Evidence Chromatin conformation capture with allele-specific reporters and ZBTB3 analysis; co-IP, ubiquitination assays and Clec2d-/- mice with Candida infection

    PMID:36869052 PMID:37872182

    Open questions at the time
    • Functional difference between IRF5-short and full-length isoforms mechanistically incomplete
    • Whether CLEC2D-driven MyD88 degradation generalizes beyond β-glucan/TLR2 contexts unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The E3 ligase mediating the K63-linked ubiquitination required for IRF5 activation, and a unifying structural model explaining how phosphorylation, ubiquitination, dimerization, and cofactor selection (PU.1, RelA, IRF4/IRF8, KAP1) are integrated across cell types, remain undefined.
  • No K63 E3 ligase identified despite ubiquitination being mechanistically central
  • No integrated structural model of the activated IRF5 dimer with cofactors
  • Determinants directing IRF5 to activating versus repressive target genes unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-5357801 Programmed Cell Death 2
Partners
IKBKBIRAK4LYNMYD88RELATASLTRAF6TRIM28
Complex memberships
Myddosome (MyD88/IRF5/IRF4)TASL-SLC15A4 complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 IRF5 physically interacts with MyD88 and TRAF6, and TLR activation via the TLR-MyD88 pathway results in nuclear translocation of IRF5 to activate transcription of proinflammatory cytokine genes (IL-6, IL-12, TNF-α); Irf5−/− mice show severely impaired cytokine induction by TLR ligands and resistance to lethal endotoxin shock. Irf5−/− mouse genetics, co-immunoprecipitation (IRF5 with MyD88/TRAF6), nuclear translocation assay, cytokine measurement in vivo and in vitro Nature High 15665823
2002 IRF5 contains a constitutive-activation domain (aa 410–489), an autoinhibitory domain (aa 490–539), and two functional nuclear localization signals (N- and C-terminal). Serine residues 477 and 480 are critical phosphorylation sites required for IRF5 transactivation in virus-infected cells; Ser→Ala mutations dramatically reduced phosphorylation and transcriptional activity. Deletion mutagenesis, site-directed mutagenesis, transient transfection reporter assays, phosphorylation analysis Molecular and cellular biology High 12138184
2004 IRF5 subcellular localization is controlled by a functional CRM1-dependent nuclear export signal (NES); mutation of two leucine residues in the NES results in constitutive nuclear accumulation. IRF5 is phosphorylated by IKKε and TBK1 in co-transfected cells, but this phosphorylation does not lead to nuclear localization or activation of IRF5. CRM1 inhibitor (leptomycin B), NES mutagenesis, subcellular fractionation/imaging, co-transfection kinase assays The Journal of biological chemistry High 15556946
2009 IKKα phosphorylates IRF5 and induces IRF5 dimerization; however, this phosphorylation exerts an inhibitory effect on IRF5 transcriptional activity by blocking K63-linked ubiquitination that is required for IRF5 activity. Alkaline phosphatase interacts with IRF5 and causes its dephosphorylation, suggesting an autoregulatory loop. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, reporter gene assay Cellular signalling Medium 19786094
2014 IKKβ phosphorylates IRF5 at serine 445 (S446 in human IRF5 isoform 1) in response to TLR and RIG-I-like receptor stimulation. A point mutation of Ser445 abolished IRF5 activation and cytokine production. IKKβ depletion or pharmacological inhibition prevented IRF5 phosphorylation. In vitro kinase assay with recombinant IKKβ, mass spectrometry phosphosite identification, phospho-specific antibody, site-directed mutagenesis, siRNA knockdown, pharmacological inhibition Proceedings of the National Academy of Sciences of the United States of America High 25326420
2014 IKKβ phosphorylates IRF5 at Ser462 in myeloid cells, inducing IRF5 dimerization and nuclear translocation. The IRF5[Ser462Ala] mutant failed to translocate to the nucleus after TLR7 stimulation. TAK1 acts as an upstream activator of IKKβ in this pathway. IKKβ-mediated IRF5 phosphorylation is required for IFNβ production in plasmacytoid dendritic cells. In vitro kinase assay (IKKβ phosphorylating IRF5 at Ser462), site-directed mutagenesis, siRNA knockdown of IKKβ and TAK1, pharmacological inhibition, nuclear translocation imaging Proceedings of the National Academy of Sciences of the United States of America High 25326418
2011 IRF5 directly activates transcription of IL-12p40, IL-12p35, and IL-23p19 genes and represses the IL-10 gene in M1 macrophages. IRF5 expression is reversibly induced by inflammatory stimuli and its high expression is characteristic of M1 macrophages, contributing to macrophage polarization plasticity. Chromatin immunoprecipitation (ChIP) at target gene promoters, IRF5 overexpression, gene expression profiling, macrophage polarization assays Nature immunology High 21240265
2014 IRF5 recruits to regulatory elements of inflammatory genes in LPS-stimulated macrophages using a composite PU.1:ISRE motif in vivo. IRF5 physically interacts with RelA (NF-κB p65), and this IRF5:RelA interaction is required for regulation of a subset of key inflammatory genes. The RelA:IRF5 interaction domain was mapped. Genome-wide ChIP-seq, protein:DNA microarrays (in vitro DNA binding), co-immunoprecipitation, gene expression profiling in IRF5- and RelA-deficient macrophages Cell reports High 25159141
2002 IRF5 is a direct transcriptional target of p53: a p53-binding site in exon 2 of the IRF5 gene binds p53 protein (EMSA), drives p53-dependent reporter activity, and IRF5 mRNA is induced by DNA damage (γ-irradiation, UV, adriamycin) in a p53-dependent manner. Differential display, EMSA, heterologous reporter assay, DNA damage induction in p53+/+ vs p53−/− cells Oncogene High 11973653
2010 IRF5 directly regulates plasma cell commitment by binding to an IRF site in the Prdm1 promoter and stimulating transcription of Blimp-1 (encoded by Prdm1), a master regulator of plasma cell differentiation. Irf5−/− mice develop age-related splenomegaly with accumulation of CD19+B220− B cells and decreased plasma cells, and ectopic IRF5 reconstitutes Blimp-1 expression. Irf5−/− mouse genetics, ChIP (IRF5 binding to Prdm1 promoter), reporter assay, ectopic expression rescue, flow cytometry Proceedings of the National Academy of Sciences of the United States of America High 20176957
2012 IRF5 directly binds to the IRF site in the ikzf1 (Ikaros) promoter and inhibits IRF8-mediated transcriptional activation of ikzf1, thereby reducing Ikaros expression and enabling IgG2a/c class switching in B cells. IRF5-deficient mice have attenuated IgG2a/c responses, which is cell-intrinsically dependent on IRF5 in B cells. Irf5−/− mouse genetics, SCID reconstitution, ChIP (IRF5 binding to ikzf1 promoter), reporter assay, in vitro class-switching assay Genes and immunity High 22535200
2008 IRF5 is required for death receptor (Fas/CD95) signaling in a cell-type-specific manner: Irf5−/− mice are resistant to hepatic apoptosis induced by Fas-activating antibody. IRF5 functions upstream of caspase 8 activation in Fas-DR signaling. TRAIL also activates IRF5 phosphorylation and nuclear translocation, leading to transactivation of death receptor signaling components. Irf5−/− mouse model, in vivo Fas-activating antibody challenge, caspase 8 activation assay, IRF5 phosphorylation and nuclear translocation analysis Proceedings of the National Academy of Sciences of the United States of America High 18268344 19028697
2010 Both HDACs and histone acetyltransferases (HATs) associate with IRF5; HDAC activity is required for IRF5-mediated transactivation of ISRE, IFNA, and IL6 promoters (but not TNFα). IRF5 phosphorylation is dependent on HAT association, resulting in IRF5 acetylation. Virus triggers dynamic conversion of an IRF5-mediated silencing complex to an activating complex at target promoters. Co-immunoprecipitation (IRF5 with HDAC1, Sin3a, HATs), HDAC inhibitor (TSA) treatment, reporter assay, domain mapping Journal of immunology Medium 20935208
2009 The KSHV-encoded vIRF-3 physically interacts with cellular IRF5 via a central double helix motif, inhibiting IRF5 binding to interferon-responsive promoter elements and blocking IRF5-mediated transcriptional transactivation and apoptosis induction. Co-immunoprecipitation, reporter assay, vIRF-3 silencing, domain mutagenesis The Journal of biological chemistry Medium 19129183
2012 KAP1/TRIM28 is an IRF5-interacting protein (identified by affinity purification/mass spectrometry) that acts as a transcriptional co-repressor of IRF5 function. The interaction interface maps to the N-terminus of IRF5 (DNA-binding domain plus intrinsically disordered region). IRF5 also forms complexes with methyltransferase SETDB1. KAP1 knockdown in human M1 macrophages potentiates IRF5-mediated TNF expression. Affinity purification coupled to mass spectrometry, co-immunoprecipitation, domain mapping, siRNA knockdown, gene expression assay Immunobiology Medium 22995936
2016 Lyn kinase physically interacts with IRF5 and inhibits K63-linked ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, suppressing IRF5 transcriptional activity independently of Lyn's kinase activity. Monoallelic deletion of Irf5 alleviates hyperproduction of cytokines in Lyn−/− dendritic cells. Co-immunoprecipitation, ubiquitination assay, kinase-dead Lyn mutant analysis, Lyn−/−Irf5+/− genetic compound mouse Immunity High 27521268
2016 Upon NOD2 stimulation in human macrophages, IRF5 binds RIP2, IRAK1, and TRAF6, and is required for optimal Akt2 activation, which drives expression of glycolytic pathway genes, HIF1A, and M1 polarization. IRF5 disease-risk variants (rs2004640/rs2280714 TT/TT) confer increased Akt2 activation and glycolysis. Co-immunoprecipitation (IRF5 with RIP2/IRAK1/TRAF6), siRNA knockdown, Akt2 kinase assay, gene expression analysis, human macrophage genotyping Cell reports Medium 27545875
2014 IRF5 directly binds the P2rx4 gene promoter in microglia upon fibronectin stimulation, driving de novo P2X4R expression. IRF8 is an upstream regulator of IRF5 expression in spinal microglia, defining an IRF8→IRF5 transcriptional axis. Irf5−/− mice fail to upregulate spinal P2X4R after peripheral nerve injury and show resistance to neuropathic pain hypersensitivity. ChIP (IRF5 binding to P2rx4 promoter), Irf5−/− mouse genetics, behavioral pain assays, IRF8/IRF5 expression analysis Nature communications High 24818655
2013 IRF5 and IRF7 (along with IRF3) coordinately regulate the type I IFN and ISG response in myeloid dendritic cells downstream of MAVS signaling. In Irf3×Irf5×Irf7 triple-KO mDCs, essentially no ISG induction was detected after WNV infection or TLR stimulation, equivalent to Mavs−/− mDCs, establishing an MAVS→IRF5 signaling link independent of IRF3 and IRF7. Triple-KO mouse genetics (Irf3−/−×Irf5−/−×Irf7−/−), microarray transcriptomics, in vitro infection assays, in vivo pathogenesis studies PLoS pathogens High 23300459
2020 TASL (encoded by CXorf21) interacts with the endolysosomal transporter SLC15A4 and contains a conserved pLxIS motif that mediates recruitment and activation of IRF5. Loss of TASL specifically impairs IRF pathway activation (IRF5) by TLR7, TLR8, and TLR9, without affecting NF-κB or MAPK signaling, identifying TASL as an innate immune adaptor linking endolysosomal TLRs to IRF5. TASL/SLC15A4 deletion in primary and transformed human immune cells, TASL mutagenesis (pLxIS motif), co-immunoprecipitation, cytokine/signaling assays Nature High 32433612
2021 PYK2 (PTK2B) phosphorylates IRF5 and is required for endogenous IRF5 activation in macrophages. PYK2-deficient macrophages and pharmacological PYK2 inhibition (defactinib) reduce IRF5 activation and inflammatory gene expression, and defactinib reduces pro-inflammatory cytokines in human colon biopsies from ulcerative colitis patients. Kinase inhibitor library screen, PYK2-deficient macrophages, defactinib pharmacological inhibition, transcriptomic profiling, ex vivo human colon biopsies, mouse colitis model Nature communications High 34795257
2017 IRAK4 kinase activity controls IRF5 activation in the TLR-MyD88 pathway: IRAK4 inhibition abolishes IRF5 nuclear translocation and prevents IRF5 binding to inflammatory cytokine promoters. IRAK4 acts through TAK1→IKKβ→IRF5 phosphorylation, while NF-κB nuclear translocation is not blocked by IRAK4 inhibition. Selective IRAK4 inhibitor in human primary monocytes, ChIP (IRF5 at cytokine promoters), transcriptomics, signaling pathway analysis The Journal of biological chemistry High 28924041
2018 IRF5 homodimer DNA-binding specificity was characterized by protein-binding microarrays; IRF5 homodimers do not bind the ISRE-variants present in IFN gene VREs, due to a critical specificity-determining residue. Mutational analysis reveals this residue inhibits IRF5 binding to IFN promoter ISRE-variants, distinguishing IRF5 from IRF3/IRF7 homodimers. Protein-binding microarrays (PBMs), site-directed mutagenesis, reporter gene assay Nucleic acids research High 29361124
2015 IRF5 directly binds promoters of TGFβ1 (TGFB1) in adipose tissue macrophages and represses its transcription; genome-wide gene expression analysis in Irf5-deficient mice placed TGFβ1 as a direct IRF5 target, linking IRF5 to adipose tissue expansion and insulin sensitivity during obesity. Genome-wide gene expression analysis (ChIP/RNA-seq implied), Irf5−/− mouse model on high-fat diet, adipose tissue macrophage isolation Nature medicine Medium 25939064
2014 BCR-ABL kinase interacts with IRF5 in CML cells and induces tyrosine phosphorylation of IRF5, reducing its transcriptional activity. Imatinib treatment partially restores IRF5 transcriptional activity. A BCR-ABL consensus site mutant (IRF5Y104F) retains significant tyrosine phosphorylation, suggesting additional phosphorylation sites or downstream pathways. Co-immunoprecipitation (IRF5-BCR-ABL), phosphotyrosine immunoblot, imatinib treatment, site-directed mutagenesis, reporter assay, cell proliferation assay Carcinogenesis Medium 24445143
2011 IRF4 negatively regulates IRF5 at the transcriptional level by binding to the IRF5 promoter, repressing its reporter activity; IRF4 knockdown leads to high IRF5 expression and growth inhibition in EBV-transformed B cells, while knockdown of IRF5 rescues IRF4 knockdown-mediated growth inhibition. ChIP (IRF4 binding to IRF5 promoter), reporter assay, siRNA knockdown, ectopic overexpression, cell growth assay The Journal of biological chemistry Medium 21454650
2006 IRF5 is not activated by viral infection directly (unlike IRF3), as assessed by phosphorylation, dimerization, nuclear translocation, CBP binding, and DNA recognition assays. However, ectopic expression of TBK1 or IKKε does activate IRF5. Constitutively active IRF5 promotes apoptosis that is inhibited by Bcl-xL but not dominant-negative FADD, placing IRF5 apoptosis in a FADD-independent pathway. Phosphorylation assay, nuclear translocation assay, dimerization assay, CBP binding assay, DNA binding assay, apoptosis assay with Bcl-xL and DN-FADD Journal of immunology Medium 16751392
2015 Higher basal IRF5 protein levels in female pDCs correlate with higher TLR7-mediated IFN-α production. Delivery of recombinant IRF5 into human primary pDCs directly increases TLR7-mediated IFN-α secretion. Genetic ablation of Esr1 (estrogen receptor 1) in hematopoietic cells or DC lineage reduces Irf5 mRNA in pDCs and IFN-α production, establishing ESR1-mediated transcriptional regulation of IRF5. Recombinant IRF5 protein delivery into primary human pDCs, conditional Esr1 KO mice, mRNA correlation analysis, IFN-α secretion assay Journal of immunology Medium 26519527
2020 IRF5 promotes differentiation of Ly6Chi monocytes into CD11c+ macrophages in the colon and controls production of antimicrobial and inflammatory mediators. IRF5 deficiency in mononuclear phagocytes ameliorates Helicobacter hepaticus-induced colitis, established via bone marrow chimera and single-cell RNA-sequencing. Irf5−/− mouse genetics, MNP-conditional IRF5 deletion, bone marrow chimera, single-cell RNA-sequencing, H. hepaticus colitis model Science immunology High 32444476
2022 CXCL4 costimulation synergistically activates TBK1 and IKKε, which are repurposed toward an inflammatory response via coupling with IRF5, leading to amplified inflammatory gene transcription. This CXCL4+TLR8 costimulation induces chromatin remodeling and de novo enhancer activation associated with inflammatory genes in human monocytes/macrophages. TBK1/IKKε/IRF5 signaling assays, ChIP-seq (chromatin remodeling), ATAC-seq (de novo enhancers), cytokine production assay in human monocytes/macrophages Nature communications High 35701499
2023 The autoimmune pleiotropic SNP rs4728142 modulates IRF5 alternative promoter usage: the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner via chromatin looping mediated by ZBTB3, promoting IRF5-short transcript expression at the risk allele and resulting in IRF5 overactivation and M1 macrophage polarization. Chromatin conformation capture (chromatin looping assay), allele-specific reporter assay, ZBTB3 functional analysis, IRF5 transcript quantification, macrophage polarization assay Nature communications High 36869052
2019 IRF5 and IRF4 form a regulatory axis in microglia controlling pro- and anti-inflammatory responses after cerebral ischemia: down-regulation of IRF5 increases IRF4 expression and enhances M2 activation, while down-regulation of IRF4 increases IRF5 and M1 activation. The two IRFs mutually suppress each other in an oscillating pattern. siRNA knockdown, lentiviral overexpression, conditional KO (cKO), middle cerebral artery occlusion stroke model, flow cytometry, RT-PCR, multiplex cytokine analysis Proceedings of the National Academy of Sciences of the United States of America High 31892541
2021 IRAK4 phosphorylates both IRF5 and IRF4 in microglia and forms a Myddosome complex with MyD88/IRF5/IRF4. IRAK4 inhibition reduces IRF5/IRF4 phosphorylation and nuclear translocation, quenches microglial pro-inflammatory responses, and increases neuronal viability after ischemia. Co-immunoprecipitation (Myddosome complex), Western blot for phospho-IRF5/IRF4, IRAK4 inhibitor (ND2158), SIM-A9 microglial cell line and primary microglia, OGD model Cells Medium 33573200
2019 IRF5 directly binds promoters of M1 macrophage-associated genes Ccl4, Ccl5, Tnf, and Il12b in myeloid cells during necrotizing enterocolitis, as shown by chromatin immunoprecipitation. Myeloid-specific Irf5 deficiency prevents experimental NEC by inhibiting M1 macrophage polarization and reducing intestinal epithelial apoptosis. ChIP (IRF5 binding to Ccl4, Ccl5, Tnf, Il12b promoters), myeloid-specific Irf5 KO, murine NEC model, immunohistochemistry Mucosal immunology High 31086271
2018 IRF5 drives TLR7-mediated IFN-α production in plasmacytoid dendritic cells and inflammatory cytokine production in myeloid cells downstream of TLR7 and possibly RIG-I, but independently of type I IFN production and virus replication. Human iPSC-derived DCs with biallelic IRF5 mutations show impaired virus-induced inflammatory cytokine production. Irf5−/− mouse in vivo IAV infection model, human iPSC with biallelic IRF5 mutations (iPSC-DCs and macrophages), CyTOF, cytokine assays Journal of virology High 32075938
2021 B cell receptor and TLR7 signaling synergize to promote IRF5 phosphorylation and increase IRF5 protein expression through independently regulated mechanisms. TLR7-dependent IRF5 nuclear translocation is reduced in B cells from IRF5-heterozygous mice. IRF5 drives IL-6 and TNF-α production in B cells, required for germinal center responses, and a critical threshold of IRF5 in B cells is required for lupus pathogenesis. Conditional B cell-specific Irf5 KO, IRF5 phosphorylation assay, nuclear translocation imaging, IL-6/TNF-α production assay, multiple murine lupus models JCI insight High 34197340
2020 IRF5 in CD4+ T cells is required for the optimal assembly of the TCR-initiated signaling complex and downstream signaling, and binds to promoters of Th1- and Th17-associated transcription factors and cytokines at later timepoints. IRF5 also regulates chemokine receptor-initiated signaling and T cell migration. Irf5-deficient CD4+ T cells show reduced Th1/Th17 cytokines and increased Th2 cytokines in vivo. T cell-conditional IRF5 deletion, TCR signaling complex immunoprecipitation, ChIP (IRF5 binding to Th1/Th17 gene promoters), migration assay, colitis model Cell reports High 32610123
2020 Cell-penetrating peptides (CPPs) designed to disrupt IRF5 homodimerization directly bind to endogenous IRF5, are cell permeable, and inhibit IRF5-mediated IFN-α production in plasmacytoid dendritic cells. CPP activity corresponds to reduced nuclear phospho-Ser462 IRF5 without affecting overall pIRF5 levels, placing CPP action downstream of phosphorylation at the dimerization step. Biochemical binding assay, live-cell imaging, IRF5 homodimerization assay, IFN-α production assay, flow cytometry for nuclear pIRF5 Science advances Medium 32440537
2023 CLEC2D forms homodimers and heterodimers with TLR2; both dimeric forms mediate β-glucan-induced ubiquitination and degradation of MyD88, inhibiting IRF5 activation and IL-12 production. Clec2d-deficient female mice show increased IL-12 production and resistance to Candida albicans infection. Co-immunoprecipitation (CLEC2D-TLR2 dimerization), quantitative ligand binding assay, ubiquitination assay, Clec2d−/− mouse model, C. albicans infection model, cytokine assays Nature communications High 37872182

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nature immunology 1058 21240265
2005 Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 809 15665823
2013 IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling. PLoS pathogens 256 23300459
2002 Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes. Molecular and cellular biology 211 12138184
2015 Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women. Journal of immunology (Baltimore, Md. : 1950) 209 26519527
2004 Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection. The Journal of biological chemistry 186 15308637
2020 TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature 178 32433612
2014 Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. Nature communications 169 24818655
2019 Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes. Proceedings of the National Academy of Sciences of the United States of America 154 31892541
2015 Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nature medicine 151 25939064
2007 Association of an IRF5 gene functional polymorphism with Sjögren's syndrome. Arthritis and rheumatism 133 18050197
2002 Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Oncogene 133 11973653
2008 Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations. Journal of medical genetics 121 18285424
2013 IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators of inflammation 112 24453413
2015 Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. Oncogene 96 26279299
2014 IRF5:RelA interaction targets inflammatory genes in macrophages. Cell reports 92 25159141
2016 Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity. Immunity 89 27521268
2016 IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation. Cell reports 89 27545875
2014 Protein kinase IKKβ-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells. Proceedings of the National Academy of Sciences of the United States of America 88 25326418
2014 IKKβ is an IRF5 kinase that instigates inflammation. Proceedings of the National Academy of Sciences of the United States of America 88 25326420
2018 Advances and challenges in targeting IRF5, a key regulator of inflammation. The FEBS journal 87 30199605
2010 Critical role of IRF-5 in regulation of B-cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 87 20176957
2017 IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice. JCI insight 76 28515358
2018 DNA-binding landscape of IRF3, IRF5 and IRF7 dimers: implications for dimer-specific gene regulation. Nucleic acids research 72 29361124
2013 IRF-5 and NF-κB p50 co-regulate IFN-β and IL-6 expression in TLR9-stimulated human plasmacytoid dendritic cells. European journal of immunology 71 23616277
2010 Differential requirement of histone acetylase and deacetylase activities for IRF5-mediated proinflammatory cytokine expression. Journal of immunology (Baltimore, Md. : 1950) 71 20935208
2020 IRF5 guides monocytes toward an inflammatory CD11c+ macrophage phenotype and promotes intestinal inflammation. Science immunology 70 32444476
2008 IRF-5 is a mediator of the death receptor-induced apoptotic signaling pathway. The Journal of biological chemistry 70 19028697
2020 Inhibition of IRF5 hyperactivation protects from lupus onset and severity. The Journal of clinical investigation 69 32897883
2017 IRAK4 kinase activity controls Toll-like receptor-induced inflammation through the transcription factor IRF5 in primary human monocytes. The Journal of biological chemistry 67 28924041
2009 The Kaposi's Sarcoma-associated Herpesvirus-encoded vIRF-3 Inhibits Cellular IRF-5. The Journal of biological chemistry 63 19129183
2009 Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome. Arthritis and rheumatism 63 19644876
2006 Differential activation of IFN regulatory factor (IRF)-3 and IRF-5 transcription factors during viral infection. Journal of immunology (Baltimore, Md. : 1950) 63 16751392
2012 KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages. Immunobiology 62 22995936
2011 Epigenetic silencing of IRF7 and/or IRF5 in lung cancer cells leads to increased sensitivity to oncolytic viruses. PloS one 62 22194884
2018 Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia. Molecular therapy. Nucleic acids 60 29858055
2010 Gender-dependent expression of murine Irf5 gene: implications for sex bias in autoimmunity. Journal of molecular cell biology 59 20802013
2004 A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization. The Journal of biological chemistry 59 15556946
2008 A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis. Proceedings of the National Academy of Sciences of the United States of America 58 18268344
2007 The genetics and biology of Irf5-mediated signaling in lupus. Autoimmunity 57 18075793
2008 Interferon regulatory factors IRF5 and IRF7 inhibit growth and induce senescence in immortal Li-Fraumeni fibroblasts. Molecular cancer research : MCR 55 18505922
2018 B Cell-Intrinsic Role for IRF5 in TLR9/BCR-Induced Human B Cell Activation, Proliferation, and Plasmablast Differentiation. Frontiers in immunology 54 29367853
2015 IRF-5-Mediated Inflammation Limits CD8+ T Cell Expansion by Inducing HIF-1α and Impairing Dendritic Cell Functions during Leishmania Infection. PLoS pathogens 52 26046638
2015 Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis. Proceedings of the National Academy of Sciences of the United States of America 50 26598674
2014 IRF5-mediated signaling and implications for SLE. Clinical immunology (Orlando, Fla.) 50 24928322
2011 Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population. Rheumatology (Oxford, England) 50 22039224
2024 Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway. International journal of nanomedicine 48 38469055
2020 Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway. Cells 48 32806763
2018 Regulation and role of the transcription factor IRF5 in innate immune responses and systemic lupus erythematosus. International immunology 48 29860420
2012 Unique contribution of IRF-5-Ikaros axis to the B-cell IgG2a response. Genes and immunity 47 22535200
2006 Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis. Arthritis and rheumatism 46 17133578
2022 Inflammatory Microenvironment-Responsive Nanomaterials Promote Spinal Cord Injury Repair by Targeting IRF5. Advanced healthcare materials 43 36165212
2021 The IKZF1-IRF4/IRF5 Axis Controls Polarization of Myeloma-Associated Macrophages. Cancer immunology research 43 33563611
2020 T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation. Cell reports 43 32610123
2019 Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization. Mucosal immunology 43 31086271
2013 RNA-Seq for enrichment and analysis of IRF5 transcript expression in SLE. PloS one 42 23349905
2020 Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients. Cells 40 32188105
2012 Gene-gene and gene-sex epistatic interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in systemic lupus erythematosus. PloS one 39 23236436
2016 A critical role for IRF5 in regulating allergic airway inflammation. Mucosal immunology 38 27759022
2020 IRF5 genetic risk variants drive myeloid-specific IRF5 hyperactivation and presymptomatic SLE. JCI insight 37 31877114
2022 CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes. Nature communications 36 35701499
2012 IRF5 promotes the proliferation of human thyroid cancer cells. Molecular cancer 34 22507190
2009 The gene and virus-induced expression of IRF-5 in grass carp Ctenopharyngodon idella. Veterinary immunology and immunopathology 34 19896215
2018 IRF5-mediated immune responses and its implications in immunological disorders. International reviews of immunology 33 29985675
2012 IRF5 gene polymorphisms in melanoma. Journal of translational medicine 33 22909381
2011 Interferon regulatory factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation. The Journal of biological chemistry 33 21454650
2009 IKKalpha negatively regulates IRF-5 function in a MyD88-TRAF6 pathway. Cellular signalling 33 19786094
2021 miR-31 from adipose stem cell-derived extracellular vesicles promotes recovery of neurological function after ischemic stroke by inhibiting TRAF6 and IRF5. Experimental neurology 32 33460643
2020 Specific enhancer selection by IRF3, IRF5 and IRF9 is determined by ISRE half-sites, 5' and 3' flanking bases, collaborating transcription factors and the chromatin environment in a combinatorial fashion. Nucleic acids research 31 31799619
2019 FcγR-TLR Cross-Talk Enhances TNF Production by Human Monocyte-Derived DCs via IRF5-Dependent Gene Transcription and Glycolytic Reprogramming. Frontiers in immunology 31 31024565
2019 Increased Adipose Tissue Expression of Interferon Regulatory Factor (IRF)-5 in Obesity: Association with Metabolic Inflammation. Cells 31 31718015
2010 Association of IRF5 gene polymorphisms and lupus nephritis in a Chinese population. Nephrology (Carlton, Vic.) 31 21040166
2021 TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation. Science advances 30 33523878
2018 IRF-5 Promotes Cell Death in CD4 T Cells during Chronic Infection. Cell reports 30 30067973
2017 Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma. The Journal of biological chemistry 30 29079574
2021 Monoallelic IRF5 deficiency in B cells prevents murine lupus. JCI insight 28 34197340
2019 Coordination between innate immune cells, type I IFNs and IRF5 drives SLE pathogenesis. Cytokine 28 31130331
2018 Diverse mechanisms of IRF5 action in inflammatory responses. The international journal of biochemistry & cell biology 28 29578052
2022 Detection of neutrophil extracellular traps in patient plasma: method development and validation in systemic lupus erythematosus and healthy donors that carry IRF5 genetic risk. Frontiers in immunology 27 35958624
2021 Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation. Nature communications 27 34795257
2014 Gene-gene interactions of IRF5, STAT4, IKZF1 and ETS1 in systemic lupus erythematosus. Tissue antigens 27 24697319
2023 An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping. Nature communications 26 36869052
2018 IRF5 Is Required for Bacterial Clearance in Human M1-Polarized Macrophages, and IRF5 Immune-Mediated Disease Risk Variants Modulate This Outcome. Journal of immunology (Baltimore, Md. : 1950) 26 30593537
2020 IRF5 Promotes Influenza Virus-Induced Inflammatory Responses in Human Induced Pluripotent Stem Cell-Derived Myeloid Cells and Murine Models. Journal of virology 25 32075938
2014 IRF5 is a target of BCR-ABL kinase activity and reduces CML cell proliferation. Carcinogenesis 25 24445143
2011 A meta-analysis of the association of IRF5 polymorphism with systemic lupus erythematosus. International journal of immunogenetics 25 21834935
2021 Phosphorylation of Microglial IRF5 and IRF4 by IRAK4 Regulates Inflammatory Responses to Ischemia. Cells 24 33573200
2019 Modulation of macrophage subtypes by IRF5 determines osteoclastogenic potential. Journal of cellular physiology 24 31127629
2013 IRF5, IRF8, and IRF7 in human pDCs - the good, the bad, and the insignificant? European journal of immunology 24 23828296
2021 IRF5 Acts as a Potential Therapeutic Marker in Inflammatory Bowel Diseases. Inflammatory bowel diseases 23 32737976
2021 Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe-/- mice. Molecular metabolism 23 33991749
2020 Potential T Cell-Intrinsic Regulatory Roles for IRF5 via Cytokine Modulation in T Helper Subset Differentiation and Function. Frontiers in immunology 23 32582209
2018 IRF5 Is a Key Regulator of Macrophage Response to Lipopolysaccharide in Newborns. Frontiers in immunology 23 30050534
2015 Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 23 26294277
2008 Association of IRF5 gene polymorphisms with rheumatoid arthritis in a Tunisian population. Scandinavian journal of rheumatology 23 18752149
2023 Shexiang Tongxin Dropping Pill alleviates M1 macrophage polarization-induced inflammation and endothelial dysfunction to reduce coronary microvascular dysfunction via the Dectin-1/Syk/IRF5 pathway. Journal of ethnopharmacology 22 37290736
2023 C-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity. Nature communications 22 37872182
2020 Overexpression of miR-133a-3p inhibits fibrosis and proliferation of keloid fibroblasts by regulating IRF5 to inhibit the TGF-β/Smad2 pathway. Molecular and cellular probes 22 32205184
2020 Inhibition of IRF5 cellular activity with cell-penetrating peptides that target homodimerization. Science advances 22 32440537
2018 Differential and Overlapping Immune Programs Regulated by IRF3 and IRF5 in Plasmacytoid Dendritic Cells. Journal of immunology (Baltimore, Md. : 1950) 20 30297339

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