Affinage

IRF5

Interferon regulatory factor 5 · UniProt Q13568

Length
498 aa
Mass
56.0 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF5 is a master transcription factor of innate and adaptive immunity that integrates TLR-MyD88 signaling to drive proinflammatory cytokine production, M1 macrophage polarization, and type I interferon responses. In its inactive state IRF5 resides in the cytoplasm; upon TLR stimulation, it is recruited to endolysosomes via the TASL–SLC15A4 adaptor complex and activated through sequential phosphorylation by IKKβ at Ser445 and PYK2, K63-linked ubiquitination by Pellino-1, and homodimerization, leading to CRM1-regulated nuclear translocation where it directly binds promoters of IL-12, IL-23p19, TNF-α, and IL-6 while repressing IL-10 and TGFB1 (PMID:15665823, PMID:25326420, PMID:32433612, PMID:28746869, PMID:21240265, PMID:25939064). IRF5 activity is negatively regulated by IKKα-mediated inhibitory phosphorylation that blocks K63-ubiquitination, Lyn kinase-dependent suppression of ubiquitination, KAP1/TRIM28–SETDB1 chromatin silencing at target loci, and TRIM21-mediated proteasomal degradation (PMID:19786094, PMID:27521268, PMID:22995936, PMID:25084355). Beyond myeloid cells, IRF5 promotes B-cell terminal differentiation by directly activating Prdm1 (Blimp-1), regulates IgG2a/c class switching through Ikaros repression, drives P2X4R expression in spinal microglia to mediate neuropathic pain, and is required for Fas-induced hepatic apoptosis (PMID:20176957, PMID:22535200, PMID:24818655, PMID:18268344).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2002 High

    Mapping of IRF5's domain architecture—including constitutive-activation, autoinhibitory, and NLS domains—and identification of Ser477/Ser480 as phosphorylation sites critical for transcriptional activation established the structural framework for understanding signal-dependent IRF5 regulation.

    Evidence Deletion and site-directed mutagenesis with reporter assays in virus-infected cells

    PMID:12138184

    Open questions at the time
    • Identity of the kinase(s) phosphorylating Ser477/480 was unknown
    • Crystal structure of autoinhibitory domain not determined
    • Relevance to TLR-driven (vs. viral) activation not tested
  2. 2004 High

    Discovery of a functional CRM1-dependent nuclear export signal in IRF5, with adjacent phosphorylatable residues controlling nuclear accumulation, revealed that IRF5 subcellular localization is actively regulated by a phosphorylation-export switch rather than simply by nuclear import.

    Evidence Leptomycin B treatment, NES mutagenesis, co-transfection kinase assays, subcellular fractionation

    PMID:15556946

    Open questions at the time
    • Physiological kinase for NES-proximal sites not identified
    • Relationship between NES phosphorylation and C-terminal activation-domain phosphorylation unclear
  3. 2005 High

    Placing IRF5 as a direct transducer of TLR-MyD88-TRAF6 signaling resolved how pattern-recognition receptors activate proinflammatory cytokine transcription; Irf5−/− mice showed severely impaired cytokine responses to multiple TLR ligands and resistance to lethal shock.

    Evidence Co-immunoprecipitation of IRF5-MyD88-TRAF6, nuclear translocation assays, Irf5−/− knockout mice with in vivo cytokine measurement

    PMID:15665823 PMID:15695821

    Open questions at the time
    • Direct kinase responsible for IRF5 activation downstream of TRAF6 was unidentified
    • Whether IRF5 activation requires ubiquitination was unknown
    • Selectivity among TLR pathways not fully resolved
  4. 2008 High

    Demonstration that IRF5 is required for Fas-induced hepatic apoptosis—acting upstream of caspase-8 and JNK—extended IRF5's function beyond cytokine transcription to cell death regulation in a cell-type-specific manner.

    Evidence Irf5−/− mice challenged with anti-Fas antibody, caspase-8/JNK activity assays, cell-type-specific apoptosis comparisons

    PMID:18268344

    Open questions at the time
    • Direct transcriptional targets of IRF5 in the apoptotic program not identified
    • Mechanism linking IRF5 to caspase-8 activation not established
  5. 2009 Medium

    IKKα was shown to phosphorylate IRF5 and promote dimerization but paradoxically inhibit IRF5 transcriptional activity by blocking K63-linked ubiquitination, establishing a negative regulatory phosphorylation and revealing that K63-ubiquitination is essential for IRF5 function.

    Evidence Co-immunoprecipitation, in vitro kinase assay, K63-ubiquitination assays, reporter assays

    PMID:19786094

    Open questions at the time
    • Identity of the E3 ligase mediating K63-ubiquitination was unknown
    • Specific IKKα phosphorylation sites on IRF5 not mapped
    • Single-lab finding at the time
  6. 2009 High

    IRF5 was placed in the NOD2-RIP2-TBK1 pathway for type I IFN induction in response to M. tuberculosis peptidoglycan, broadening IRF5's role beyond TLR signaling to intracellular bacterial sensing.

    Evidence Genetic epistasis with Irf5−/−, Irf3−/−, Tbk1-deficient mice, IFN measurement after M. tuberculosis infection

    PMID:19578435

    Open questions at the time
    • Direct biochemical interaction of IRF5 with NOD2/RIP2 components not shown
    • Phosphorylation mechanism in this pathway undefined
  7. 2010 High

    Identification of IRF5 as a direct transcriptional activator of Prdm1 (Blimp-1) established a role for IRF5 in B-cell terminal differentiation to plasma cells, distinct from its myeloid functions.

    Evidence Irf5−/− mice, ChIP and EMSA showing IRF5 binding to Prdm1 promoter, B-cell differentiation assays with reconstitution

    PMID:20176957

    Open questions at the time
    • Whether IRF5 activation in B cells requires the same TLR-MyD88 axis was unclear
    • Signaling events controlling IRF5 in B-cell differentiation not mapped
  8. 2010 Medium

    Discovery that IRF5 associates with both HDACs and HATs, undergoing a phosphorylation-dependent switch from an HDAC silencing complex to an activating HAT complex, revealed an epigenetic mechanism for IRF5-dependent gene regulation.

    Evidence Co-immunoprecipitation of IRF5 with HDAC1/SMRT/NCoR/Sin3a/HATs, trichostatin A treatment, reporter assays

    PMID:20935208

    Open questions at the time
    • Specific HAT responsible for IRF5 acetylation not identified
    • Functional consequence of IRF5 acetylation on target genes not fully explored
    • Single-lab observation
  9. 2011 High

    ChIP and global expression profiling established IRF5 as the key transcription factor driving M1 macrophage polarization, directly activating IL-12p40/p35 and IL-23p19 while repressing IL-10, thereby shaping TH1-TH17 responses.

    Evidence IRF5 overexpression and knockout in macrophages, ChIP at IL-12 and IL-10 promoters, global gene expression profiling

    PMID:21240265

    Open questions at the time
    • Genome-wide IRF5 binding map (ChIP-seq) not yet available at this point
    • Mechanism of IL-10 repression by IRF5 not determined
  10. 2012 Medium

    KAP1/TRIM28 was identified as an IRF5-interacting corepressor that recruits SETDB1 to deposit H3K9me3 at the TNF locus, revealing a chromatin-level negative regulatory mechanism for IRF5 target genes.

    Evidence Affinity purification/mass spectrometry, Co-IP, KAP1 siRNA knockdown, ChIP for H3K9me3

    PMID:22995936

    Open questions at the time
    • Genome-wide extent of KAP1-SETDB1-mediated silencing of IRF5 targets unknown
    • Whether the IRF5-KAP1 interaction is signal-regulated not determined
  11. 2012 High

    IRF5 was shown to regulate IgG2a/c class switching by binding the ikzf1 (Ikaros) promoter and antagonizing IRF8-mediated Ikaros transcription, extending IRF5's B-cell role from plasma cell differentiation to isotype control.

    Evidence SCID reconstitution with Irf5−/− B cells, ChIP at ikzf1 promoter, in vitro class switching assays

    PMID:22535200

    Open questions at the time
    • Whether this mechanism operates in human B cells not shown
    • IRF5-IRF8 competition at the Ikaros promoter not structurally characterized
  12. 2014 High

    IKKβ was identified as the direct activating kinase for IRF5, phosphorylating Ser445 as confirmed by mass spectrometry and phosphospecific antibody; S445A mutation abolished IRF5 activation, resolving the long-sought identity of the signal-dependent kinase.

    Evidence In vitro kinase reconstitution with recombinant IKKβ, mass spectrometry, phosphospecific antibody, S445A mutagenesis, siRNA/inhibitor validation

    PMID:25326420

    Open questions at the time
    • Whether additional phosphorylation events are required alongside Ser445 not fully resolved
    • Relationship between IKKβ Ser445 phosphorylation and the previously identified Ser477/480 sites unclear
  13. 2014 High

    IRF5 was found to directly activate P2rx4 transcription in spinal microglia downstream of nerve injury, within an IRF8→IRF5 transcriptional cascade, establishing IRF5 as a mediator of neuropathic pain hypersensitivity.

    Evidence ChIP of IRF5 at P2rx4 promoter, Irf5−/− and Irf8−/− mice with behavioral pain assays, fibronectin stimulation

    PMID:24818655

    Open questions at the time
    • Whether the TASL/IKKβ activation mechanism operates in microglia not tested
    • Full set of IRF5 target genes in microglia not determined
  14. 2014 Medium

    TRIM21 was shown to mediate TLR7-dependent proteasomal degradation of IRF5, with alternative splice isoforms (exon 6 insertion) resisting degradation, linking IRF5 isoform expression to protein stability and autoimmune risk.

    Evidence TRIM21 overexpression/knockdown, proteasome inhibitors, isoform comparison, TLR7 stimulation

    PMID:25084355

    Open questions at the time
    • Direct TRIM21-mediated ubiquitination of IRF5 not reconstituted in vitro
    • Structural basis for isoform-specific resistance not determined
  15. 2015 High

    IRF5 was shown to directly repress TGFB1 transcription in adipose tissue macrophages; Irf5 deficiency shifted macrophage polarization toward M2, improving insulin sensitivity in obese mice, extending IRF5's role to metabolic inflammation.

    Evidence Irf5−/− mice on high-fat diet, ChIP at TGFB1 promoter, genome-wide expression analysis, metabolic phenotyping

    PMID:25939064

    Open questions at the time
    • Whether IRF5 directly binds TGFB1 regulatory elements or acts through intermediaries at the chromatin level
    • Upstream signals activating IRF5 in adipose tissue macrophages not fully characterized
  16. 2015 High

    Estrogen receptor alpha was identified as a transcriptional regulator of IRF5, with females showing higher basal IRF5 levels in pDCs correlating with enhanced IFN-α production, providing a molecular basis for sex-biased autoimmune susceptibility.

    Evidence Esr1 conditional knockout mice, recombinant IRF5 delivery into human pDCs, flow cytometry, RT-PCR

    PMID:20802013 PMID:26519527

    Open questions at the time
    • Direct ERα binding to the IRF5 promoter not demonstrated by ChIP
    • Whether estrogen regulation of IRF5 applies beyond pDCs and B cells not explored
  17. 2016 High

    Lyn kinase was identified as a negative regulator that physically interacts with IRF5 and suppresses its ubiquitination and phosphorylation in a kinase-activity-independent manner; genetic epistasis showed Lyn−/−-driven SLE is IRF5-dependent.

    Evidence Co-IP, kinase-dead Lyn mutants, ubiquitination assays, Lyn−/− × Irf5+/− genetic epistasis mice

    PMID:27521268

    Open questions at the time
    • Structural basis for Lyn-IRF5 interaction unknown
    • Whether Lyn acts as a scaffold or competitive binding partner not resolved
  18. 2017 High

    Pellino-1 was identified as the E3 ubiquitin ligase that K63-ubiquitinates IRF5 to promote its nuclear translocation in M1 macrophages, filling the long-standing gap of which ligase mediates activating ubiquitination.

    Evidence Co-IP, K63-specific ubiquitination assay, nuclear fractionation, Pellino-1 knockout macrophages, in vivo metabolic phenotype

    PMID:28746869

    Open questions at the time
    • Specific lysine residues on IRF5 targeted by Pellino-1 not mapped
    • Whether Pellino-1 is the sole E3 ligase or whether redundant ligases exist
  19. 2017 High

    The IRAK4→TAK1→IKKβ kinase cascade was shown to be specifically required for IRF5 nuclear translocation (but not NF-κB translocation) downstream of TLR7/8 in human monocytes, delineating the IRF5 activation pathway from NF-κB at the level of IRAK4 kinase activity.

    Evidence Selective IRAK4 kinase inhibitor, ChIP, nuclear fractionation, transcriptomics in primary human monocytes

    PMID:28924041

    Open questions at the time
    • Whether IRAK4 phosphorylates IRF5 directly or only through intermediaries not biochemically distinguished
  20. 2020 High

    TASL (CXorf21), identified by CRISPR screen, was established as the endolysosomal adaptor that bridges SLC15A4 to IRF5 via a pLxIS motif, specifically required for IRF5 but not NF-κB/MAPK activation downstream of TLR7/8/9, solving how IRF5 is recruited to the signaling platform.

    Evidence Genome-wide CRISPR screen, Co-IP, pLxIS mutagenesis, endolysosomal localization, multiple human immune cell types

    PMID:32433612

    Open questions at the time
    • Structural basis of TASL-IRF5 interaction not resolved
    • Whether TASL is required in all IRF5-activating pathways (e.g., NOD2, Fas) unknown
  21. 2020 Medium

    Cell-penetrating peptides targeting the IRF5 homodimerization interface inhibited nuclear translocation of phosphorylated IRF5 without affecting phosphorylation itself, demonstrating that dimerization is a discrete, targetable step downstream of phosphorylation and upstream of nuclear entry.

    Evidence Biochemical binding assays, nuclear fractionation with phosphospecific antibody, pDC IFN-α production assays

    PMID:32440537

    Open questions at the time
    • Peptide selectivity over other IRF family members not fully characterized
    • In vivo efficacy and pharmacokinetics not established
  22. 2021 High

    PYK2 (PTK2B) was identified as an additional activating kinase for IRF5; PYK2-deficient macrophages phenocopied IRF5 deficiency transcriptomically, and pharmacological PYK2 inhibition reduced inflammation in human ulcerative colitis biopsies.

    Evidence Kinase inhibitor library screen, PYK2−/− macrophages, transcriptomics, IRF5 phosphorylation assays, human tissue validation

    PMID:34795257

    Open questions at the time
    • Specific IRF5 residues phosphorylated by PYK2 not mapped
    • Relationship between PYK2 and IKKβ phosphorylation of IRF5 (parallel vs. sequential) unresolved
  23. 2022 High

    CXCL4 costimulation with TLR8 was shown to repurpose TBK1-IKKε toward IRF5 (rather than IRF3) activation, driving de novo enhancer formation at inflammatory loci and NLRP3 inflammasome engagement, revealing context-dependent kinase-IRF substrate switching.

    Evidence Kinase activation assays, IRF5 translocation, ChIP-seq for chromatin remodeling, NLRP3 inhibitor, primary human monocytes/macrophages

    PMID:35701499

    Open questions at the time
    • Mechanism determining TBK1-IKKε substrate selectivity (IRF5 vs. IRF3) not molecularly defined
    • Whether CXCL4-driven IRF5 activation uses TASL unknown
  24. 2023 High

    The autoimmune risk variant rs4728142 was shown to regulate IRF5 expression through allele-specific chromatin looping mediated by the zinc-finger protein ZBTB3, promoting alternative promoter usage and IRF5 overactivation that drives M1 polarization, connecting non-coding genetic variation to IRF5 function.

    Evidence Chromosome conformation capture (3C), CRISPR-Cas9 allele editing, ZBTB3 binding validation, macrophage polarization assays

    PMID:36869052

    Open questions at the time
    • Whether ZBTB3 regulation of IRF5 extends beyond macrophages to B cells and pDCs not tested
    • Full enhancer landscape of the IRF5 locus under different stimulation conditions not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of IRF5 autoinhibition and dimerization, the precise lysine residues targeted by K63-ubiquitination, how IKKβ and PYK2 phosphorylation events are coordinated, whether TASL is required across all IRF5-activating pathways, and the molecular mechanism by which IRF5 represses genes such as IL-10 and TGFB1.
  • No crystal structure of full-length IRF5 in autoinhibited or active states
  • Ubiquitination sites on IRF5 not mapped by mass spectrometry
  • Mechanism of transcriptional repression by IRF5 remains undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 3 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 11 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 1
Complex memberships
Myddosome (MyD88-IRAK4-IRF5)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 IRF5 interacts with and is activated by MyD88 and TRAF6 downstream of TLR signaling; TLR activation results in nuclear translocation of IRF5 to activate proinflammatory cytokine gene transcription (IL-6, IL-12, TNF-α). Irf5-/- mice show severely impaired cytokine induction by various TLR ligands and resistance to lethal shock. Co-immunoprecipitation, nuclear translocation assays, Irf5-/- knockout mouse model with in vivo cytokine measurement Nature High 15665823
2005 IRF5 is selectively activated by TLR7 and TLR8 signaling (not TLR3), requiring MyD88, IRAK1, and TRAF6 for its activation. Ectopic IRF5 expression enabled type I interferon production in response to TLR7 signaling; siRNA knockdown of IRF5 reduced TLR7-induced IFN production. Overexpression, siRNA knockdown, reporter assays, dominant-negative mutants The Journal of biological chemistry High 15695821
2002 IRF5 contains a constitutive-activation domain (aa 410–489), an autoinhibitory domain (aa 490–539), and functional nuclear localization signals in both N- and C-termini. Phosphorylation of Ser477 and Ser480 is critical for IRF5 activation; S477A/S480A mutations dramatically decreased phosphorylation and transactivation in virus-infected cells. Deletion mutagenesis, site-directed mutagenesis, transfection reporter assays, nuclear localization assays Molecular and cellular biology High 12138184
2004 IRF5 possesses a functional CRM1-dependent nuclear export signal (NES); mutation of two leucine residues in the NES or phosphomimetic substitution of adjacent Ser/Thr residues results in constitutive nuclear IRF5 localization, indicating phosphorylation of these residues contributes to nuclear accumulation. IKKε and TBK1 phosphorylate IRF5 but this does not lead to nuclear localization or activation. Leptomycin B (CRM1 inhibitor) treatment, NES mutagenesis, co-transfection kinase assays, subcellular fractionation/imaging The Journal of biological chemistry High 15556946
2009 IKKα phosphorylates IRF5 and induces IRF5 dimer formation but exerts an inhibitory effect on IRF5 transcriptional activation; IKKα-mediated phosphorylation inhibits K63-linked ubiquitination of IRF5, which is required for IRF5 activity. Alkaline phosphatase interacts with IRF5 and causes its dephosphorylation, providing an autoregulatory loop. Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, reporter assays Cellular signalling Medium 19786094
2014 IKKβ phosphorylates IRF5 at Ser445 (S446 in human isoform 1) in response to TLR and RIG-I-like receptor stimulation, as confirmed by mass spectrometry and a phosphospecific antibody. In vitro reconstitution showed recombinant IKKβ phosphorylates IRF5 at Ser445; S445A point mutation abolished IRF5 activation and cytokine production. Depletion or pharmacological inhibition of IKKβ prevented IRF5 phosphorylation. In vitro kinase assay with recombinant proteins, mass spectrometry, phosphospecific antibody, site-directed mutagenesis, siRNA/inhibitor depletion Proceedings of the National Academy of Sciences of the United States of America High 25326420
2017 IRAK4 kinase activity controls TLR7/8-induced IRF5 nuclear translocation and binding to inflammatory cytokine promoters in human monocytes, acting upstream via TAK1 and IKKβ phosphorylation; IRAK4 inhibition blocked IKKβ phosphorylation and IRF5 nuclear translocation without affecting NF-κB nuclear translocation. Selective IRAK4 kinase inhibitor, ChIP, nuclear fractionation, transcriptomics in primary human monocytes The Journal of biological chemistry High 28924041
2020 TASL (encoded by CXorf21) is an innate immune adaptor that localizes to endolysosomes via interaction with SLC15A4 and contains a conserved pLxIS motif that recruits and activates IRF5. Loss of TASL or SLC15A4 specifically abolishes IRF5 pathway activation (without affecting NF-κB/MAPK) downstream of TLR7, TLR8, and TLR9. Genome-wide CRISPR screen, Co-IP, extensive mutagenesis of TASL pLxIS motif, endolysosomal localization studies, primary and transformed human immune cells Nature High 32433612
2016 Lyn kinase physically interacts with IRF5 and inhibits its ubiquitination and phosphorylation in the TLR-MyD88 pathway, suppressing IRF5 transcriptional activity in a manner independent of Lyn's kinase activity. Lyn-/- mice develop SLE-like disease that is alleviated by monoallelic deletion of Irf5. Co-immunoprecipitation, kinase-dead Lyn mutants, ubiquitination assays, genetic epistasis (Lyn-/- x Irf5+/- mice), dendritic cell cytokine assays Immunity High 27521268
2017 Pellino-1 (E3 ubiquitin ligase) interacts with IRF5 in the cytoplasm and promotes K63-linked ubiquitination of IRF5, increasing its nuclear translocation in M1 macrophages; LPS/IFN-γ-induced M1 polarization requires Pellino-1, and Pellino-1 deficiency attenuates M1 polarization and improves glucose tolerance in obese mice. Co-immunoprecipitation, ubiquitination assay (K63-specific), nuclear fractionation, Pellino-1 knockout macrophages, in vivo metabolic assays Cell reports High 28746869
2010 Both HDACs and HATs (histone acetyltransferases) associate with IRF5, altering its transactivation ability. HDAC activity is required for ISRE, IFNA, and IL6 promoter transactivation but not TNFα. HAT association with IRF5 is dependent on IRF5 phosphorylation and results in IRF5 acetylation. Virus triggers conversion of an IRF5-HDAC silencing complex to an activating HAT complex on target gene promoters. Co-immunoprecipitation (HDAC1, SMRT/NCoR, Sin3a, HATs with IRF5), HDAC inhibitor trichostatin A, reporter assays, domain mapping Journal of immunology Medium 20935208
2012 KAP1/TRIM28 was identified as an IRF5-interacting protein by affinity purification/mass spectrometry; the N-terminus of IRF5 (DNA-binding domain plus disordered region) is the interaction interface. IRF5 also forms complexes with methyltransferase SETDB1. KAP1 knockdown potentiated IRF5-mediated TNF and M1 macrophage marker expression, linked to SETDB1-dependent H3K9me3 deposition at the TNF locus. Affinity purification/mass spectrometry, Co-IP, domain mapping, KAP1 siRNA knockdown, ChIP (H3K9me3) Immunobiology Medium 22995936
2014 TRIM21 (TRIpartite motif 21) regulates IRF5 stability in a TLR7-dependent manner; IRF5 undergoes proteasomal degradation following TLR7 activation in a TRIM21-dependent process. IRF5 isoforms generated by alternative splicing (exon 6 insertion) are resistant to TRIM21-mediated degradation, linking isoform expression to stability and SLE-associated function. TRIM21 overexpression/knockdown, proteasome inhibitors, isoform comparison, TLR7 stimulation assays PloS one Medium 25084355
2009 Rotavirus NSP1 induces proteasome-dependent degradation of IRF5 (as well as IRF3 and IRF7), acting as a broad-spectrum antagonist of IRF function by recognizing a common element of IRF proteins. Proteasome inhibitor assays, virus infection studies comparing wild-type vs. NSP1-defective rotaviruses, western blotting Journal of virology Medium 17301153
2009 KSHV-encoded vIRF-3 directly interacts with cellular IRF5, inhibiting IRF5 DNA binding to interferon-responsive promoter elements and blocking IRF5-mediated transcriptional activation; a central double helix motif in vIRF-3 is sufficient to abrogate both DNA binding and transactivation by IRF5. vIRF-3 also antagonized IRF5-mediated p21 promoter activation. Co-immunoprecipitation, EMSA (electrophoretic mobility shift assay), reporter assays, domain deletion mapping, vIRF-3 siRNA silencing The Journal of biological chemistry High 19129183
2011 IRF5 directly activates transcription of IL-12p40, IL-12p35, and IL-23p19 genes and represses the IL-10 gene in M1 macrophages, contributing to macrophage polarization to a pro-inflammatory phenotype and driving TH1-TH17 responses. Global gene expression analysis confirmed IRF5 upregulates M1 and downregulates M2 macrophage markers. IRF5 overexpression in macrophages, ChIP (IRF5 binding to IL-12 and IL-10 promoters), IRF5-/- macrophage analysis, global gene expression profiling Nature immunology High 21240265
2010 IRF5 is required for B-cell terminal differentiation; IRF5 directly stimulates transcription of Prdm1 (encoding Blimp-1, the master regulator of plasma cell differentiation) by binding to the IRF site in the Prdm1 promoter. Irf5-/- mice develop age-related splenomegaly with accumulation of CD19+B220- B cells and decreased plasma cells. Irf5-/- knockout mice, EMSA/ChIP (IRF5 binding to Prdm1 promoter), ectopic IRF5 reconstitution, B-cell differentiation assays Proceedings of the National Academy of Sciences of the United States of America High 20176957
2012 IRF5 regulates IgG2a/c class switching in B cells by decreasing Ikaros expression; IRF5 binds the IRF site in the ikzf1 (Ikaros) promoter and inhibits IRF8-mediated transcriptional activation of Ikaros, downregulating Ikaros levels to increase IgG2a/c switching. SCID reconstitution with Irf5-/- B cells, ChIP (IRF5 at ikzf1 promoter), in vitro class switching assays, reporter assays, IRF5 reconstitution in Irf5-/- B cells Genes and immunity High 22535200
2014 IRF5, induced in spinal microglia after peripheral nerve injury, directly binds the promoter region of the P2rx4 gene to drive de novo expression of P2X4R upon fibronectin stimulation. Irf5-/- mice lack spinal P2X4R upregulation after nerve injury and show substantial resistance to pain hypersensitivity. IRF5 expression in microglia is regulated by IRF8 (IRF8-IRF5 transcriptional axis). ChIP (IRF5 at P2rx4 promoter), Irf5-/- mice, behavioral pain assays, IRF8-/- mice, microglia fibronectin stimulation Nature communications High 24818655
2008 IRF5 is required for Fas (CD95)-induced hepatic apoptosis in a cell-type-specific manner, acting at a stage preceding caspase-8 and JNK activation. Irf5-/- mice are resistant to Fas-antibody-induced hepatic apoptosis and lethality. IRF5 is also required for apoptosis in dendritic cells activated by CpG but not in thymocytes or embryonic fibroblasts. Irf5-/- knockout mice, in vivo Fas-antibody administration, caspase-8 and JNK activity assays, cell-type-specific apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 18268344
2009 IRF5 (along with NOD2 and RIP2) is required for type I interferon induction in response to M. tuberculosis peptidoglycan via intraphagosomal recognition; this pathway is TBK1- and IRF5-dependent but only partially dependent on IRF3, distinguishing it from the bacterial DNA-sensing pathway that requires IRF3 entirely. Irf5-/- and Irf3-/- knockout mice, Tbk1 deficiency, genetic epistasis, IFN measurement after M. tuberculosis infection PLoS pathogens High 19578435
2015 IRF5 directly inhibits transcription of the TGFB1 gene in adipose tissue macrophages, as shown by genome-wide analysis and ChIP. Loss of Irf5 in macrophages leads to enhanced TGFB1 expression, accumulation of alternatively activated macrophages, and improved insulin sensitivity in obese mice. Irf5-/- knockout mice on high-fat diet, ChIP (IRF5 at TGFB1 promoter), genome-wide gene expression analysis, metabolic phenotyping Nature medicine High 25939064
2015 IRF5 activated by TLR4 binds to promoters of various SSc-associated genes including those governing fibroblast activation, endothelial-mesenchymal transition, and immune polarization. Irf5-/- mice are protected from bleomycin-induced dermal and pulmonary fibrosis with suppression of multiple SSc-associated pathological events. Irf5-/- knockout mice, bleomycin SSc model, ChIP (IRF5 at promoters of SSc-associated genes), TLR4 activation studies Proceedings of the National Academy of Sciences of the United States of America High 26598674
2010 Gender-based differences in IRF5 expression depend on estrogen receptor alpha (ERα); estradiol treatment increases Irf5 mRNA and protein levels, ERα-/- female mice express lower Irf5, and splenic B cells from female mice have more nuclear IRF5 than males, suggesting ERα-driven transcriptional regulation of IRF5. ERα-/- knockout mice, estradiol treatment of splenic cells, nuclear fractionation, RT-PCR, western blotting Journal of molecular cell biology Medium 20802013
2015 In plasmacytoid dendritic cells, basal IRF5 levels are higher in females than males, positively correlate with IFN-α secretion, and are regulated by estrogen receptor 1 (ESR1); genetic ablation of Esr1 in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression and IFN-α production. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. Esr1 conditional knockout mice, recombinant IRF5 protein delivery into primary human pDCs, flow cytometry, RT-PCR, correlation analysis Journal of immunology High 26519527
2011 IRF4 directly binds to the IRF5 promoter in vivo and in vitro and negatively regulates IRF5 transcription; knockdown of IRF4 leads to elevated IRF5 expression and growth inhibition in EBV-transformed B cells, whereas IRF5 knockdown rescues IRF4-knockdown-mediated growth inhibition. ChIP (IRF4 at IRF5 promoter), EMSA, reporter assays, IRF4/IRF5 siRNA knockdown, cell growth assays The Journal of biological chemistry Medium 21454650
2021 PYK2 (PTK2B) phosphorylates IRF5 and is required for endogenous IRF5 activation; PYK2-deficient macrophages display impaired IRF5 activation and reduced inflammatory gene expression. The PYK2 inhibitor defactinib phenocopies IRF5 deficiency transcriptomically in macrophages and reduces pro-inflammatory cytokines in human colon biopsies from ulcerative colitis patients. Kinase inhibitor library screen, PYK2-/- macrophages, transcriptomics, IRF5 phosphorylation assays, human colitis biopsy ex vivo assay, mouse colitis model Nature communications High 34795257
2022 CXCL4 synergizes with TLR8 to activate TBK1 and IKKε, which are repurposed toward an inflammatory response via coupling with IRF5 (rather than IRF3); costimulation activates the NLRP3 inflammasome and induces chromatin remodeling with de novo enhancers at inflammatory genes. The TBK1-IKKε-IRF5 axis drives amplified IL-1β production. Kinase activation assays, IRF5 translocation/activation assays, ChIP-seq (chromatin remodeling), NLRP3 inhibitor studies, primary human monocytes/macrophages Nature communications High 35701499
2020 IRF5 undergoes homodimerization upon stimulation and nuclear translocation as phosphorylated dimers to mediate proinflammatory gene transcription; cell-penetrating peptides (CPPs) targeting the IRF5 homodimerization interface are cell permeable, bind endogenous IRF5, and inhibit IFN-α production in pDCs by reducing nuclear phosphorylated IRF5 levels without affecting total pIRF5, placing CPP action downstream of phosphorylation. Biochemical binding assays, imaging (CPP localization), nuclear fractionation with phosphospecific IRF5 antibody, pDC IFN-α production assays Science advances Medium 32440537
2011 In murine pDCs, myxoma virus-induced type I IFN and cytokine production requires TLR9/MyD88, IRF5 and IRF7 (but not IRF3, MAVS, or TRIF), and the IFNAR-mediated positive feedback loop; PI3K and Akt are also required pharmacologically. pDCs from IRF5-/-, IRF7-/-, IRF3-/-, MyD88-/-, MAVS-/-, IFNAR1-/- knockout mice, pharmacological PI3K/Akt inhibitors, IFN/cytokine measurement Journal of virology High 21835795
2019 IRF5 controls differentiation of Ly6Chi monocytes into CD11c+ macrophages in the colon and controls production of antimicrobial and inflammatory mediators by these cells; IRF5 deficiency in MNPs ameliorates H. hepaticus-induced colitis immunopathology, as confirmed by bone marrow chimera and single-cell RNA-sequencing. Irf5-/- global and myeloid-conditional knockout mice, colitis model, bone marrow chimeras, single-cell RNA-sequencing, flow cytometry Science immunology High 32444476
2021 IRAK4 phosphorylates both IRF5 and IRF4 in microglia, forming a Myddosome complex with MyD88/IRF5/IRF4; phosphorylated IRF5 and IRF4 translocate to the nucleus. IRAK4 inhibition blocks these phosphorylation events, quenches pro-inflammatory microglial responses, and increases neuronal viability after ischemia. Co-immunoprecipitation (Myddosome complex), IRAK4 inhibitor (ND2158), phosphorylation western blot, nuclear translocation assays, primary microglia and SIM-A9 cells, OGD model Cells Medium 33573200
2023 An autoimmune pleiotropic variant rs4728142 regulates IRF5 alternative promoter usage through allele-specific chromatin looping; the structural regulator ZBTB3 mediates the allele-specific chromatin loop to promote IRF5-short transcript expression at the risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Chromosome conformation capture (3C), CRISPR-Cas9 allele editing, dual-luciferase reporter assays, ZBTB3 binding validation, macrophage polarization assays Nature communications High 36869052

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 1053 21240265
2005 Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 804 15665823
2007 Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proceedings of the National Academy of Sciences of the United States of America 382 17412832
2005 The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. The Journal of biological chemistry 323 15695821
2009 NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS pathogens 227 19578435
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) 205 26519527
2020 TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature 173 32433612
2007 Rotavirus NSP1 inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3, IRF5, and IRF7. Journal of virology 172 17301153
2014 Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. Nature communications 166 24818655
2007 Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus. Human molecular genetics 162 18063667
2015 Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nature medicine 151 25939064
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 147 31892541
2007 An insertion-deletion polymorphism in the interferon regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases. Human molecular genetics 143 17881657
2007 Association of an IRF5 gene functional polymorphism with Sjögren's syndrome. Arthritis and rheumatism 133 18050197
2018 Regulation of age-associated B cells by IRF5 in systemic autoimmunity. Nature immunology 126 29483597
2008 Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations. Journal of medical genetics 120 18285424
2006 Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation. Human molecular genetics 104 17189288
2007 Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus. Arthritis and rheumatism 97 17393452
2015 Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. Oncogene 94 26279299
2009 BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4. Arthritis and rheumatism 94 19877059
2016 Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity. Immunity 88 27521268
2014 IKKβ is an IRF5 kinase that instigates inflammation. Proceedings of the National Academy of Sciences of the United States of America 87 25326420
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 86 20176957
2018 Advances and challenges in targeting IRF5, a key regulator of inflammation. The FEBS journal 85 30199605
2017 IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice. JCI insight 76 28515358
2020 The GM-CSF-IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses. The Journal of experimental medicine 75 32970801
2010 Differential requirement of histone acetylase and deacetylase activities for IRF5-mediated proinflammatory cytokine expression. Journal of immunology (Baltimore, Md. : 1950) 70 20935208
2020 IRF5 guides monocytes toward an inflammatory CD11c+ macrophage phenotype and promotes intestinal inflammation. Science immunology 69 32444476
2020 Inhibition of IRF5 hyperactivation protects from lupus onset and severity. The Journal of clinical investigation 68 32897883
2009 Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus. The Journal of rheumatology 67 19567624
2017 IRAK4 kinase activity controls Toll-like receptor-induced inflammation through the transcription factor IRF5 in primary human monocytes. The Journal of biological chemistry 66 28924041
2011 Critical role of IRF-5 in the development of T helper 1 responses to Leishmania donovani infection. PLoS pathogens 63 21253574
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
2012 KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages. Immunobiology 61 22995936
2011 Epigenetic silencing of IRF7 and/or IRF5 in lung cancer cells leads to increased sensitivity to oncolytic viruses. PloS one 61 22194884
2014 TRIpartite motif 21 (TRIM21) differentially regulates the stability of interferon regulatory factor 5 (IRF5) isoforms. PloS one 59 25084355
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
2018 Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia. Molecular therapy. Nucleic acids 57 29858055
2007 The genetics and biology of Irf5-mediated signaling in lupus. Autoimmunity 56 18075793
2008 Interferon regulatory factors IRF5 and IRF7 inhibit growth and induce senescence in immortal Li-Fraumeni fibroblasts. Molecular cancer research : MCR 55 18505922
2020 MicroRNA-22-3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5. Journal of neurochemistry 50 32406529
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
2012 Pleiotropic IFN-dependent and -independent effects of IRF5 on the pathogenesis of experimental lupus. Journal of immunology (Baltimore, Md. : 1950) 50 22422888
2011 Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis. The Journal of rheumatology 50 21239750
2014 IRF5-mediated signaling and implications for SLE. Clinical immunology (Orlando, Fla.) 49 24928322
2012 Monocytes from Irf5-/- mice have an intrinsic defect in their response to pristane-induced lupus. Journal of immunology (Baltimore, Md. : 1950) 49 22933628
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
2015 IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis. Journal of immunology (Baltimore, Md. : 1950) 48 25595782
2018 Regulation and role of the transcription factor IRF5 in innate immune responses and systemic lupus erythematosus. International immunology 47 29860420
2016 IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans. JCI insight 47 27942586
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 46 38469055
2012 Unique contribution of IRF-5-Ikaros axis to the B-cell IgG2a response. Genes and immunity 46 22535200
2006 Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis. Arthritis and rheumatism 46 17133578
2021 The IKZF1-IRF4/IRF5 Axis Controls Polarization of Myeloma-Associated Macrophages. Cancer immunology research 43 33563611
2022 Inflammatory Microenvironment-Responsive Nanomaterials Promote Spinal Cord Injury Repair by Targeting IRF5. Advanced healthcare materials 42 36165212
2009 Association of IRF5 polymorphisms with activation of the interferon alpha pathway. Annals of the rheumatic diseases 41 19854706
2020 Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients. Cells 40 32188105
2016 Nanoparticle-Delivered IRF5 siRNA Facilitates M1 to M2 Transition, Reduces Demyelination and Neurofilament Loss, and Promotes Functional Recovery After Spinal Cord Injury in Mice. Inflammation 40 27435985
2011 Myxoma virus induces type I interferon production in murine plasmacytoid dendritic cells via a TLR9/MyD88-, IRF5/IRF7-, and IFNAR-dependent pathway. Journal of virology 40 21835795
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 36 31877114
2017 Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity. Cell reports 36 28746869
2022 CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes. Nature communications 35 35701499
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
2019 Bisphenol A promotes macrophage proinflammatory subtype polarization via upregulation of IRF5 expression in vitro. Toxicology in vitro : an international journal published in association with BIBRA 32 31108126
2018 IRF5-mediated immune responses and its implications in immunological disorders. International reviews of immunology 32 29985675
2011 Interferon regulatory factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation. The Journal of biological chemistry 32 21454650
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
2010 Validation of IRF5 as multiple sclerosis risk gene: putative role in interferon beta therapy and human herpes virus-6 infection. Genes and immunity 30 20861862
2019 FcγR-TLR Cross-Talk Enhances TNF Production by Human Monocyte-Derived DCs via IRF5-Dependent Gene Transcription and Glycolytic Reprogramming. Frontiers in immunology 28 31024565
2019 An Allele-Specific Functional SNP Associated with Two Systemic Autoimmune Diseases Modulates IRF5 Expression by Long-Range Chromatin Loop Formation. The Journal of investigative dermatology 28 31421124
2021 Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation. Nature communications 26 34795257
2020 DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion. Frontiers in cell and developmental biology 26 33392187
2019 Coordination between innate immune cells, type I IFNs and IRF5 drives SLE pathogenesis. Cytokine 26 31130331
2018 Rheumatoid arthritis patient antibodies highly recognize IL-2 in the immune response pathway involving IRF5 and EBV antigens. Scientific reports 26 29379122
2018 Diverse mechanisms of IRF5 action in inflammatory responses. The international journal of biochemistry & cell biology 26 29578052
2014 Genetic association study of TNFAIP3, IFIH1, IRF5 polymorphisms with polymyositis/dermatomyositis in Chinese Han population. PloS one 26 25337792
2013 Four Promoters of IRF5 Respond Distinctly to Stimuli and are Affected by Autoimmune-Risk Polymorphisms. Frontiers in immunology 25 24223576
2011 A meta-analysis of the association of IRF5 polymorphism with systemic lupus erythematosus. International journal of immunogenetics 25 21834935
2023 An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping. Nature communications 24 36869052
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 24 35958624
2020 IRF5 Promotes Influenza Virus-Induced Inflammatory Responses in Human Induced Pluripotent Stem Cell-Derived Myeloid Cells and Murine Models. Journal of virology 24 32075938
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) 24 30593537
2013 IRF5, IRF8, and IRF7 in human pDCs - the good, the bad, and the insignificant? European journal of immunology 24 23828296
2011 Association of IRF5 polymorphisms with susceptibility to hemophagocytic lymphohistiocytosis in children. Journal of clinical immunology 24 21898142
2023 Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn. Journal of cellular and molecular medicine 23 37132040
2021 Phosphorylation of Microglial IRF5 and IRF4 by IRAK4 Regulates Inflammatory Responses to Ischemia. Cells 23 33573200
2021 Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe-/- mice. Molecular metabolism 23 33991749
2019 Modulation of macrophage subtypes by IRF5 determines osteoclastogenic potential. Journal of cellular physiology 23 31127629
2008 Association of IRF5 gene polymorphisms with rheumatoid arthritis in a Tunisian population. Scandinavian journal of rheumatology 23 18752149
2020 Inhibition of IRF5 cellular activity with cell-penetrating peptides that target homodimerization. Science advances 22 32440537