Affinage

IRF8

Interferon regulatory factor 8 · UniProt Q02556

Length
426 aa
Mass
48.4 kDa
Annotated
2026-04-28
100 papers in source corpus 56 papers cited in narrative 56 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRF8 (also known as ICSBP) is an IFN-γ-inducible transcription factor that serves as a master regulator of mononuclear phagocyte development and innate immune function, controlling the differentiation, identity, and activation of monocytes, macrophages, dendritic cells, microglia, NK cells, and B cells through dose-dependent engagement of lineage-specific enhancers. IRF8 heterodimerizes with PU.1, IRF-1, BATF3, NFAT, and Miz-1 at EICE, AICE, ISRE, and composite cis-elements, functioning as a transcriptional activator of IL-12, autophagy genes, and antimicrobial effectors (e.g., Nramp1) while repressing targets such as acid ceramidase, GAS2, and osteoclast programs (PMID:15947094, PMID:25775030, PMID:12904288, PMID:21487040, PMID:30721543). High IRF8 expression, controlled by stage-specific enhancers driven by RUNX-CBFβ, BATF3, and E-proteins, establishes cDC1 identity via AICE-dependent transcription, whereas graded lower levels direct monocyte or neutrophil fates; loss of IRF8 in committed cDC1s causes reprogramming toward a cDC2-like state (PMID:33603226, PMID:31406378, PMID:32795402, PMID:35830859). Biallelic loss-of-function mutations in IRF8 cause human primary immunodeficiency characterized by absence of monocytes, dendritic cells, and NK cell maturation defects (PMID:21524210, PMID:27893462).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Establishing how IRF8 transcription is induced: the gene's IFN-γ responsiveness was traced to a palindromic IFN response element in its promoter bound by STAT1, providing the first molecular link between IFN-γ signaling and IRF8 expression.

    Evidence Promoter reporter assays, gel-shift with anti-STAT1, mutagenesis in murine cells

    PMID:8321202

    Open questions at the time
    • Other trans-acting factors at the promoter not identified
    • Post-transcriptional regulation unexplored at this stage
  2. 1995 High

    Defining IRF8's modular architecture resolved how it could both repress and activate transcription: three functional domains were mapped—a DNA-binding domain, a repressor domain, and an IRF-association domain enabling heterodimerization with IRF-1 and IRF-2.

    Evidence Domain deletion/fusion constructs, EMSA, co-immunoprecipitation

    PMID:7768900

    Open questions at the time
    • Structural basis for partner selectivity unknown
    • Post-translational modifications not examined
  3. 2000 High

    The question of how macrophages produce IL-12 was answered by showing IRF8 is the principal activator of IL-12 p40 transcription, binding the Ets site of the promoter and synergizing with IRF-1, establishing IRF8 as a key innate immune effector.

    Evidence ICSBP−/− macrophage-like cells, promoter transfection, DNA affinity assay, endogenous IL-12p40 mRNA measurement

    PMID:10861061

    Open questions at the time
    • Chromatin context of IL-12 p40 regulation not addressed
    • Whether IRF8 cooperates with NFAT at this locus unknown at this point
  4. 2002 High

    IRF8's role expanded beyond macrophage activation to developmental biology: knockout mice revealed IRF8 is essential cell-intrinsically for the generation of plasmacytoid DC precursors and CD8α+ dendritic cells, placing IRF8 as a lineage-determining factor.

    Evidence ICSBP−/− mice, wild-type/KO bone marrow chimeras, flow cytometry, RT-PCR

    PMID:12393690 PMID:12461077

    Open questions at the time
    • Whether IRF8 is continuously required or only during commitment unknown
    • Stage-specific enhancer regulation not yet explored
  5. 2003 High

    IRF8's partner repertoire and target gene network were expanded: NFAT was shown to physically associate with IRF8 for IL-12 p40 induction (inhibitable by IL-10), Miz-1 was identified as a novel partner enabling Nramp1 transcription for antimicrobial defense, and IRF8 was found to suppress c-Myc via Blimp-1/METS to induce growth arrest in Bcr/Abl-transformed cells.

    Evidence Endogenous co-IP, ChIP, yeast two-hybrid (Miz-1), dominant-negative NFAT, conditional IRF8 induction in CML cells

    PMID:12876285 PMID:12904288 PMID:12933588

    Open questions at the time
    • Crystal structure of IRF8-partner complexes lacking
    • Relative contribution of each partner in different cell types unclear
  6. 2005 High

    A novel composite cis-element (IRF/Ets) was identified as the genomic signature for IRF8-PU.1 cooperative binding at macrophage differentiation genes, explaining how IRF8 activates lineage-specific targets like cystatin C and cathepsin C.

    Evidence Microarray, retroviral reporter, ChIP, promoter deletion in myeloid cells

    PMID:15947094

    Open questions at the time
    • Genome-wide catalog of EICE sites not yet available
    • Structural basis for cooperative IRF8-PU.1 DNA binding unknown
  7. 2007 High

    The BXH2 mouse IRF8 R294C mutation demonstrated that partner interaction—not DNA binding alone—dictates subset-specific DC development: the mutation abolished CD8α+ DC generation while sparing pDC development, mechanistically separating these programs.

    Evidence BXH2 mouse, EMSA showing loss of partner-dependent complexes, ChIP

    PMID:18055870

    Open questions at the time
    • Identity of the critical partner(s) lost in R294C context not fully resolved
    • Whether other hematopoietic lineages are affected unexamined
  8. 2008 High

    IRF8 was shown to modulate HSC lineage choice toward B cells by directly binding Sfpi1 (PU.1) and Ebf1 promoters—repressing PU.1 and activating Ebf1—revealing IRF8 function outside myeloid cells.

    Evidence ChIP, reporter assay, IRF8−/− HSC rescue with wild-type vs. mutant IRF8

    PMID:18799728

    Open questions at the time
    • How IRF8 coordinates myeloid vs. lymphoid lineage decisions simultaneously not resolved
  9. 2011 High

    Human disease causality was established: IRF8 mutations K108E and T80A that impair DNA binding cause primary immunodeficiency with loss of monocytes and dendritic cells, validating the mouse findings in humans.

    Evidence Patient genetic sequencing, functional transcriptional assays across multiple patients

    PMID:21524210

    Open questions at the time
    • Allelic series of partial vs. complete human IRF8 deficiency not yet characterized
    • Effect on NK cells not assessed in this study
  10. 2013 High

    Genome-wide binding data revealed IRF8 establishes enhancer landscapes (H3K4me1) with PU.1 during monocyte differentiation and operates upstream of KLF4, while separately IRF8 loss was shown to generate MDSCs suppressed via STAT3/STAT5 signaling.

    Evidence ChIP-seq in differentiating monocytes, KLF4 rescue in Irf8−/− cells, MDSC phenotyping in Irf8−/− mice with overexpression rescue

    PMID:23319570 PMID:24091328

    Open questions at the time
    • Whether IRF8-dependent enhancers are poised before or after IRF8 binding unclear
    • Direct MDSC transcriptional targets of IRF8 not cataloged
  11. 2015 High

    IRF8's function expanded to autophagy and B cell biology: IRF8 directly activates autophagy genes in macrophages essential for Listeria clearance, and with PU.1 promotes B cell identity by inducing BCL6/PAX5 while repressing AID/BLIMP-1, antagonizing IRF4-driven plasma cell differentiation.

    Evidence Irf8−/− macrophage autophagy assays with Listeria infection; conditional B cell KO with gene expression and functional differentiation assays; stochastic modeling of IRF8-IRF4 antagonism

    PMID:25288399 PMID:25775030 PMID:26437243

    Open questions at the time
    • Which autophagy genes are direct vs. indirect targets not fully resolved
    • Whether IRF8-IRF4 antagonism operates through competition for shared sites genome-wide unclear
  12. 2016 High

    Stage-specific conditional deletions revealed IRF8 acts as a continuous terminal selector for cDC1 survival, is required only during early monocyte development, and biallelic IRF8 mutations cause familial NK cell deficiency with impaired terminal maturation.

    Evidence Multiple Cre driver conditional KO mice for DC subsets and monocytes; human patient genetics with Irf8−/− mouse NK phenotyping and chimeras

    PMID:27637148 PMID:27893462

    Open questions at the time
    • Molecular targets of IRF8 in NK cell maturation not identified
    • How IRF8 requirement transitions from essential to dispensable in monocytes unknown
  13. 2018 High

    IRF8's chromatin-pioneering function was established: in progenitors (MDPs and LMPPs), IRF8 opens chromatin at DC/monocyte enhancers before associated gene expression, and in NK cells, IL-12/STAT4 signaling epigenetically remodels the Irf8 locus to drive the proliferative burst via Zbtb32.

    Evidence ATAC-seq/H3K4me1 ChIP-seq across hematopoietic development in Irf8−/− MDPs; scRNA-seq + ATAC-seq in IRF8-GFP knock-in LMPPs; conditional Irf8 KO in NK cells with MCMV infection

    PMID:29514092 PMID:29858012 PMID:30796024

    Open questions at the time
    • Whether IRF8 acts as a pioneer factor or requires pre-existing chromatin accessibility not distinguished
    • Mechanism of STAT4-dependent Irf8 locus remodeling not fully resolved
  14. 2019 High

    The cis-regulatory logic of Irf8 itself was decoded: a +41-kb enhancer (E-protein-dependent) drives Irf8 induction for cDC1 specification in CDPs, a +32-kb enhancer (BATF3-dependent) sustains expression for cDC1 maturation, and an Nfil3-Zeb2-Id2 circuit switches enhancer usage during commitment. Separately, PU.1 partner switching from IRF8 to NFATc1 during osteoclastogenesis explained how IRF8 suppresses osteoclast programs.

    Evidence CRISPR enhancer deletions with in vivo DC development; scRNA-seq of CDPs with genetic epistasis; ChIP-seq/FAIRE-seq comparing macrophages and osteoclasts during RANKL differentiation

    PMID:30721543 PMID:31406377 PMID:31406378

    Open questions at the time
    • Additional enhancers controlling Irf8 in non-DC lineages not fully mapped
    • Structural basis for PU.1 partner switching not determined
  15. 2020 High

    Dose-dependent IRF8 function was resolved at the cis-element level: high IRF8 engages BATF3 at AICE elements for cDC1-specific genes, while low IRF8 or IRF4 redundantly activates EICE-dependent common DC genes. Human allelic series confirmed that IRF8hi and IRF8lo pathways produce distinct DC/monocyte subsets.

    Evidence ChIP-seq with IRF8/IRF4 concentration titration and conditional KO; high-dimensional flow cytometry with human IRF8-deficient patients

    PMID:32735845 PMID:32795402

    Open questions at the time
    • How graded IRF8 protein levels are achieved post-transcriptionally in vivo unclear
    • AICE vs. EICE genome-wide occupancy as function of IRF8 dose not fully quantified
  16. 2021 High

    Upstream regulation of IRF8 expression was further clarified: a +56-kb RUNX-CBFβ-driven enhancer controls Irf8 throughout the myeloid lineage to set dose-dependent fate (cDC1 vs. monocyte vs. neutrophil), and in AML, ZMYND8 activates IRF8 via BRD4 at a lineage-specific enhancer, creating an AML proliferation dependency.

    Evidence In vivo enhancer deletion with ATAC-seq and quantitative IRF8 titration; ChIP-seq and ZMYND8 KO in AML cells with BRD4 co-IP

    PMID:33603226 PMID:34358447

    Open questions at the time
    • How multiple enhancers integrate to set precise IRF8 protein levels is not modeled
    • Whether the ZMYND8-IRF8 axis is specific to certain AML subtypes unclear
  17. 2022 High

    Two non-transcriptional and post-transcriptional mechanisms were discovered: phosphorylation of IRF8 at Ser151 enables a transcription-independent interaction with STING that promotes STING polymerization and innate DNA sensing, while FTO-mediated m6A demethylation of IRF8 mRNA triggers its degradation. Additionally, IRF8 loss in committed cDC1s causes their epigenetic and functional reprogramming into cDC2-like cells.

    Evidence Phosphorylation site mapping with STING co-IP and polymerization assay; m6A-seq with FTO KD/OE and mRNA stability assay; Xcr1-Cre conditional Irf8 deletion with ATAC-seq/RNA-seq

    PMID:35830859 PMID:35973990 PMID:36478193

    Open questions at the time
    • Kinase responsible for Ser151 phosphorylation not identified
    • Whether STING interaction is unique to monocytes or occurs in other IRF8-expressing cells unknown
    • m6A regulation of IRF8 confirmed only in T-ALL context
  18. 2024 High

    IRF8's role as an epigenomic regulator of microglial identity was established: IRF8 binds stepwise to enhancers with Sall1 and PU.1 in postnatal microglia to drive chromatin accessibility and DNA methylation patterns; its deletion shifts microglia toward disease-associated microglia (DAM) programs and reduces amyloid plaque engagement.

    Evidence ChIP-seq, ATAC-seq, scRNA-seq, DNA methylation profiling, constitutive and conditional Irf8 KO, 5xFAD Alzheimer's model

    PMID:39313544

    Open questions at the time
    • Whether IRF8 loss-driven DAM-like state is functionally identical to bona fide DAM unclear
    • Temporal dynamics of IRF8-Sall1-PU.1 binding during microglial maturation not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the kinase phosphorylating IRF8 at Ser151, the structural basis for IRF8's partner-dependent switch between activation and repression, how multiple distal enhancers quantitatively integrate to set precise IRF8 protein levels across lineages, and whether IRF8's transcription-independent STING interaction operates broadly across mononuclear phagocyte subsets.
  • No kinase identified for Ser151
  • No crystal structure of IRF8-PU.1 or IRF8-BATF3 complexes on DNA
  • Enhancer integration model lacking
  • STING interaction tested mainly in monocytes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 17 GO:0003677 DNA binding 9
Localization
GO:0005634 nucleus 6
Pathway
R-HSA-1266738 Developmental Biology 11 R-HSA-168256 Immune System 11 R-HSA-4839726 Chromatin organization 6 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
BATF3BRD4IRF1IRF4NFATSPI1STAT1ZBTB17

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Two IRF8 mutations (K108E and T80A) impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA, causing human primary immunodeficiency with loss of monocytes and dendritic cells. Patient genetic sequencing, functional transcriptional assays The New England journal of medicine High 21524210
2002 ICSBP/IRF8 is essential for the development of mouse type I IFN-producing cells (plasmacytoid DC precursors) and CD8α+ dendritic cells, and is required for IL-12p40 and IL-15 expression but not IL-4 in DCs. ICSBP−/− mouse phenotyping, flow cytometry, RT-PCR The Journal of experimental medicine High 12461077
2002 ICSBP/IRF8 is required intrinsically in bone marrow-derived progenitors for in vivo differentiation of CD8α+ DCs, functioning downstream of common DC progenitors, and also influences functional maturation of CD8α− DCs. ICSBP−/− mice, wild-type/ICSBP−/− bone marrow chimeras, flow cytometry Blood High 12393690
2000 ICSBP/IRF8 acts as a principal transcriptional activator of IL-12 p40 in macrophages by binding the Ets site of the IL-12 p40 promoter via protein-protein interaction, and synergizes with IRF-1 to induce IL-12 p40 expression. ICSBP−/− macrophage-like cells, promoter transfection, DNA affinity binding assay, endogenous IL-12p40 mRNA induction Journal of immunology High 10861061
1995 ICSBP/IRF8 contains at least three functional domains: a DNA-binding domain (amino acids 1-121), a transcriptional repressor domain, and an IRF-association domain enabling heterocomplex formation with IRF-1 and IRF-2 in vitro and in vivo. Domain deletion/fusion constructs (ICSBP-VP16, GAL4-ICSBP), reporter assays, EMSA, co-immunoprecipitation The Journal of biological chemistry High 7768900
1993 The murine ICSBP/IRF8 gene is induced by IFN-γ through a palindromic IFN response element (pIRE, TTCNNGGAA) in the promoter that binds the 91-kDa ISGF3α subunit (STAT1). Genomic structure analysis, promoter reporter assay, gel mobility shift assay, antibody competition Molecular and cellular biology High 8321202
2013 IRF8 loss in mice generates myeloid populations homologous to MDSCs; MDSC-inducing factors G-CSF and GM-CSF downregulate IRF8 via STAT3- and STAT5-dependent pathways, placing IRF8 as a negative regulator of MDSC development. Irf8−/− mice, IRF8 overexpression in vivo, cytokine treatment, gene expression profiling, STAT pathway analysis The Journal of clinical investigation High 24091328
2016 IRF8 acts as a terminal selector for cDC1 survival; conditional deletion shows IRF8 is required during early but not late monocyte development, and late deletion of IRF8 in pDCs alters their phenotype and gene expression, impairing type I IFN production while increasing T cell stimulatory function. Conditional Irf8fl/fl mice with multiple Cre drivers, BM chimeras, gene expression profiling Immunity High 27637148
2013 IRF8 binds promoter-proximal and distal regions genome-wide with PU.1 during monocyte differentiation, associated with enhancer formation (H3K4me1), and operates upstream of KLF4 to drive monocyte (Ly6C+) differentiation. ChIP-seq, gene expression profiling, Irf8−/− mice, KLF4 rescue experiments in Irf8−/− cell lines Blood High 23319570
2016 IRF8 and IRF1 cooperatively control macrophage transcriptional programs at basal level and after IFN-γ activation, with IRF8 operating in two major cistrome clusters together with PU.1 and STAT1 to direct antimicrobial and inflammatory gene expression. ChIP-seq, RNA-seq in IRF8 and IRF1 mutant primary macrophages, histone modification profiling The Journal of experimental medicine High 27001747
2007 The IRF8 R294C mutation (BXH2 mouse) abolishes CD8α+ DC development without impairing pDC development by preventing IRF8 interaction with partner transcription factors and blocking binding to promoters requiring partner interactions, demonstrating mechanistic separation of DC subset development. BXH2 mouse characterization, EMSA, chromatin immunoprecipitation assay Blood High 18055870
2005 IRF8 activates macrophage differentiation target genes (cystatin C, cathepsin C, lysozyme, prosaposin) through a novel cis element (GAAANN[N]GGAA) comprising a core IRF-binding and Ets-binding motif; IRF8 and PU.1 bind this element in vivo. Microarray, retroviral reporter assay, chromatin immunoprecipitation, promoter deletion analysis Blood High 15947094
2003 NFAT and ICSBP/IRF8 bind a composite element at -68 to -54 of the IL-12 p40 promoter; NFAT is required for ICSBP binding to this region, NFAT and ICSBP physically associate independent of DNA, and this association is abrogated by IL-10. Chromatin immunoprecipitation, co-immunoprecipitation of endogenous proteins, reporter assays, dominant-negative NFAT The Journal of biological chemistry High 12876285
2002 ICSBP/IRF8 and IRF-1 cooperatively stimulate murine IL-12 p40 transcription through an ISRE-like element distinct from the NF-κB and C/EBP sites in the murine promoter. Co-transfection reporter assays, promoter mutation analysis in RAW264.7 macrophages FEBS letters Medium 12417340
2002 ICSBP/IRF8 exerts dual transcriptional activity (repression or activation) depending on which partner it heterodimerizes with; the IRF association domain (IAD) of IRF8 and a PEST domain on partners mediate the interaction. Protein-protein interaction domain analysis, reporter assays Journal of interferon & cytokine research Medium 11846986
2003 ICSBP/IRF8 represses PU.1-induced Dab2 (disabled-2) promoter transactivation by binding the Dab2 promoter together with PU.1, and Dab2 overexpression promotes macrophage spreading, adhesion, and actin fiber formation. ChIP, reporter/promoter assay, overexpression in bone marrow-derived macrophages The EMBO journal Medium 11823414
2003 ICSBP/IRF8 inhibits growth of Bcr/Abl-transformed myeloid progenitor cells by activating Blimp-1 and METS/PE1 as direct target genes, which in turn repress c-Myc expression, causing growth arrest and macrophage differentiation without inhibiting Bcr/Abl kinase activity. ICSBP ectopic expression, ICSBP/estrogen receptor chimera, c-Myc mRNA measurement, Blimp-1/METS identification as direct targets Blood High 12933588
2014 IRF8 promotes neuroinflammation by enhancing αvβ8 integrin expression in APCs, thereby activating TGF-β signaling leading to Th17 cell differentiation; IRF8 also induces IL-12 and IL-23 but inhibits IL-27, and activates microglia. Irf8−/− mouse EAE model, bone marrow chimeras, gene expression analysis Immunity High 24485804
2008 IRF8 binds directly to an IRF8/Ets consensus sequence in promoters of Sfpi1 (PU.1) and Ebf1, repressing Sfpi1 and activating Ebf1 transcription, thereby modulating HSC lineage choice toward B cells. ChIP, reporter assay, IRF8−/− mice, HSC rescue with WT vs signaling-deficient IRF8 mutant Blood High 18799728
2014 The IRF8-PU.1 complex promotes B cell identity by simultaneously inducing BCL6 and PAX5 and repressing AID and BLIMP-1, thus suppressing class-switch recombination and plasma cell differentiation; this complex functions reciprocally to IRF4. Conditional knockout mice, gene expression profiling, functional differentiation assays The Journal of experimental medicine High 25288399
2015 IRF8 and PU.1 form a double-negative feedback loop with IRF4 to regulate B cell developmental bifurcation; IRF8 dampens BCR signaling, facilitates antigen-specific T cell interaction, and promotes antibody affinity maturation while antagonizing IRF4-driven plasmablast differentiation. Conditional knockout mice, genomic analysis, stochastic modeling, functional B cell assays Nature immunology High 26437243
2015 IRF8 directly activates autophagy-related genes in macrophages in response to multiple stresses (IFNγ, TLR stimulation, bacterial infection, starvation, M-CSF), promoting autophagosome formation and lysosomal fusion; Irf8−/− macrophages fail to clear Listeria monocytogenes due to deficient autophagic activity. Irf8−/− macrophages, autophagy assays (SQSTM1/ubiquitin accumulation), Listeria infection, gene expression Nature communications High 25775030
2011 IRF8 directly binds the acid ceramidase (A-CDase) promoter and represses its transcription; loss of IRF8 increases A-CDase levels, reducing ceramide accumulation and impairing Fas-mediated apoptosis in CML cells. IRF8 expression in CML is regulated by promoter DNA methylation. ChIP, A-CDase siRNA/overexpression, ceramide measurement, apoptosis assays, in vivo CML model Cancer research High 21487040
2010 ICSBP/IRF8, together with Tel and HDAC3, binds a cis element in the GAS2 promoter to repress GAS2 transcription; GAS2 inhibits calpain protease activity, and ICSBP thereby controls calpain-dependent β-catenin protein degradation in myeloid progenitors. Promoter reporter assay, ChIP, calpain activity assay, β-catenin protein measurement Molecular and cellular biology High 20679491
2018 During viral infection, NK cells upregulate IRF8 via IL-12 signaling through STAT4, which promotes epigenetic remodeling of the Irf8 locus; IRF8 then facilitates NK cell proliferative burst by promoting cell-cycle gene expression and directly controlling Zbtb32. IL-12/STAT4 signaling analysis, Irf8 locus epigenetic profiling, Irf8 conditional KO in NK cells, MCMV infection model Immunity High 29858012
2019 A +32-kb Irf8 enhancer (BATF3-dependent) is required for cDC1 maturation but not specification; a +41-kb Irf8 enhancer (previously considered pDC-specific) is transiently accessible in cDC1 progenitors and is required for Irf8 induction in CDPs and cDC1 fate specification. CRISPR/Cas9 genome editing of enhancers, chromatin profiling, in vivo DC development analysis Nature immunology High 31406378
2019 Nfil3 is required for the transition to committed cDC1 progenitors (Zeb2hi→Zeb2lo/Id2hi); this Nfil3-Zeb2-Id2 circuit blocks E-protein activity, switching Irf8 enhancer usage from the +41-kb to the +32-kb enhancer during cDC1 development. Single-cell RNA-seq of CDP, genetic epistasis among Nfil3, Id2, Zeb2, Irf8 enhancer deletion Nature immunology High 31406377
2020 High IRF8 concentrations engage BATF3 at AP1-IRF composite elements (AICEs) to activate cDC1-specific genes (e.g., Xcr1), while low IRF8 or IRF4 can redundantly activate EICE-dependent common DC genes; cDC1 identity depends on AICE-mediated transcription requiring high IRF8. ChIP-seq, conditional KO, IRF8/IRF4 concentration titration experiments Immunity High 32795402
2021 A RUNX-CBFβ-driven enhancer 56 kb downstream of the Irf8 TSS controls Irf8 expression throughout the myeloid lineage; high, low, or null IRF8 expression promotes cDC1, Ly6C+ monocyte, or neutrophil differentiation respectively through epigenetic regulation of distinct enhancer sets. In vivo enhancer deletion, ATAC-seq, conditional KO, quantitative IRF8 expression titration Nature immunology High 33603226
2018 IRF8 and PU.1 govern enhancer landscape dynamics in mononuclear phagocyte progenitors (MDPs): IRF8 is required for establishment of monocyte- and DC-specific enhancers at progenitor stages before associated gene expression, particularly for enhancers common to both lineages. ATAC-seq/H3K4me1 ChIP-seq in vivo across hematopoietic development, Irf8−/− MDPs Cell reports High 29514092
2019 IRF8 expressed in a subpopulation of LMPPs changes chromatin accessibility at DC lineage gene enhancers, biasing fate toward DCs (especially cDC1) independently of significant transcriptional changes at that stage. Single-cell RNA-seq, ATAC-seq, IRF8-GFP knock-in mice, Irf8−/− mice, in vivo transfer experiments Blood High 30796024
2022 IRF8 is required for efficient STING-mediated innate immune responses in monocytes via a transcription-independent mechanism: upon DNA sensing, IRF8 is phosphorylated at Serine 151, enabling its IRF-associated domain to associate with STING and facilitate STING polymerization and TBK1-mediated phosphorylation of STING and IRF3. IRF8 phosphorylation site mapping, co-immunoprecipitation with STING, STING polymerization assay, IRF8 KO monocytes, HSV-1 infection model Nature communications High 35973990
2022 IRF8-expressing tumor-associated macrophages (TAMs) promote CTL exhaustion in tumors by presenting cancer cell antigens to CTLs; TAM-specific IRF8 deletion prevents exhaustion of cancer-reactive CTLs and suppresses tumor growth. TAM-specific Irf8 conditional KO, murine breast cancer model, CTL exhaustion assays Immunity High 36288724
2022 IRF8 loss in committed cDC1s causes their transcriptional, functional, and epigenetic reprogramming into cDC2-like cells, independently of IRF4, associated with decreased accessibility of IRF8/Batf3/AICE-binding elements and increased cDC2-associated TF-binding sites. Xcr1-Cre conditional Irf8 deletion, ATAC-seq, RNA-seq, functional assays Immunity High 35830859
2003 IRF-8 drives Nramp1 expression in macrophages via protein-protein interaction with Miz-1 (identified by yeast two-hybrid) and PU.1, all of which bind to the Nramp1 promoter; Irf8−/− mice have low Nramp1 expression that cannot be induced, explaining susceptibility to intracellular pathogens. Yeast two-hybrid, ChIP, Irf8−/− mouse infection studies, promoter analysis The Journal of biological chemistry High 12904288
2017 USP4 physically interacts with IRF8 and stabilizes it via K48-linked deubiquitination in regulatory T cells; USP4 depletion promotes IRF8 polyubiquitination and impairs Treg suppressive function. Co-immunoprecipitation, ubiquitination assay, USP4 knockdown, Treg functional assays FEBS letters Medium 28477415
2012 miR-22 directly binds the 3'UTR of Irf8 mRNA for posttranscriptional repression, and overexpression of miR-22 enhances cDC differentiation at the expense of pDCs while reducing Irf8 mRNA abundance. Luciferase reporter assay with Irf8 3'UTR, miR-22 overexpression/knockdown, DC differentiation assays PloS one Medium 23251709
2010 IRF8 and PU.1 bind to the EICE on the NLRP3-related and IFN-signaling gene promoters in myeloid cells; siRNA knockdown of IRF8 in THP-1 cells identifies direct functional target genes including OAS1 and IRF9. siRNA knockdown, ChIP-chip, gene expression profiling Molecular immunology Medium 20573402
2021 ZMYND8 directly activates IRF8 in AML via its lineage-specific enhancer, requiring BRD4 (via ZMYND8's chromatin reader cassette binding to BRD4's ET domain); this ZMYND8-IRF8 axis is an AML dependency for proliferation. ChIP-seq, ZMYND8 KO in vitro and in vivo, BRD4 co-IP, enhancer analysis in cell lines and patient samples Molecular cell High 34358447
2021 Brd4 forms a complex with IRF8/PU.1 and binds to IRF8 and PU.1 binding motifs on Naip promoters to maintain Naip expression, which is required for NLRC4 inflammasome activation in response to Salmonella infection. Brd4 conditional KO macrophages, RNA-seq, ChIP, co-immunoprecipitation, inflammasome assays The Journal of cell biology High 33535228
2020 IRF8 promotes NLRP3 inflammasome activation during Gram-negative bacterial infection by mediating IRF3 phosphorylation required for Ifnb transcription, which in turn triggers caspase-11-dependent NLRP3 activation. Irf8−/− bone marrow-derived macrophages, Gram-negative bacterial infection, caspase-11 and gasdermin-D cleavage assays, Ifnb measurement Journal of immunology Medium 32205422
2020 PU.1 and IRF8 bind the EICE site at -309/-300 of the human NLRP3 distal promoter, and knockdown of either factor downregulates NLRP3 and diminishes LPS-induced IL-1β secretion in THP-1 macrophages. Reporter assay, EMSA, ChIP, siRNA knockdown, IL-1β ELISA Frontiers in immunology Medium 33897697
2019 PU.1 switches transcriptional partner from IRF8 (in macrophages) to NFATc1 (in osteoclasts) during RANKL-induced osteoclastogenesis; IRF8 downregulation correlates with Irf8 promoter chromatin closure and decreased expression of IRF8-target macrophage genes. ChIP-seq, FAIRE-seq, H3K4me1/H3K27ac profiling in BMMs and OCs, RANKL differentiation Journal of bone and mineral research High 30721543
2019 IRF8 G388S mutation (in conserved C-terminal motif) promotes osteoclastogenesis and fails to inhibit NFATc1-dependent transcriptional activation; genome-wide IRF8 binding in osteoclast precursors is lost with the mutation, enhancing osteoclast-specific transcripts. Functional osteoclastogenesis assays, NFATc1 reporter, ChIP-seq, Irf8+/− mice alveolar bone phenotyping Journal of bone and mineral research High 30840779
2007 IRF8 controls thymic CHRNA1 expression by binding an IRF8-binding site in the CHRNA1 promoter; a promoter variant (associated with myasthenia gravis) prevents IRF8 binding and abrogates promoter activity in thymic epithelial cells, working cooperatively with AIRE. Promoter reporter assay in thymic epithelial cells, EMSA, human genetic association across two populations Nature High 17687331
2018 IRF8 and PU.1 directly target each other's gene transcription in a positive feedback loop, and cooperatively bind IRF-ETS composite motifs on microglial activation-related genes, as verified biochemically by synergistic binding of IRF8 and PU.1 to composite-motif DNA; post-developmental deletion of either in microglia abolishes microglial activation. 3D fluorescence imaging, conditional KO in microglia, ChIP, synergistic DNA binding assay Protein & cell High 30484118
2024 IRF8 binds stepwise to enhancer regions in postnatal microglia along with Sall1 and PU.1, driving chromatin accessibility preceding microglia-specific gene expression; IRF8 is also required for microglia-specific DNA methylation patterns; deletion shifts microglia toward DAM-like gene programs and reduces amyloid plaque interaction. ChIP-seq, ATAC-seq, scRNA-seq, scATAC-seq, DNA methylation profiling, constitutive and conditional Irf8 KO, 5xFAD model Nature immunology High 39313544
2015 IRF8 is required for IL-1β expression in reactive spinal microglia via an IRF1-dependent pathway: peripheral nerve injury induces IRF8, which in turn induces IRF1, and IRF1 is required for IRF8-driven IL-1β upregulation. IRF8 lentiviral transduction in cultured microglia, IRF1 knockdown, in vivo nerve injury model with IRF8-deficient mice Journal of pharmacological sciences Medium 26318672
2015 Irf8 is required for formation of all macrophages during primitive and transient definitive hematopoiesis in zebrafish, with rescue of macrophage fate by wildtype irf8 expression in neutrophil/macrophage lineages, indicating irf8 regulates macrophage specification and survival. TALEN-mediated irf8 null zebrafish, irf8 rescue expression, lineage analysis PloS one Medium 25615614
2013 In CML, Wnt/β-catenin activation upregulates Irf8 in normal hematopoiesis, and Irf8 in turn limits oncogenic β-catenin; combined Irf8 deficiency and constitutive β-catenin activation causes CML blast crisis with elevated leukemic potential and imatinib resistance. Mouse genetics, BCR-ABL CML model, β-catenin/Irf8 double KO, gene expression profiling The Journal of experimental medicine Medium 24101380
2020 Human cDC2 heterogeneity originates from two distinct IRF8-dependent pathways: a lymphoid-primed IRF8hi pathway produces pDCs, cDC1s, and DC2s, while an IRF8lo common myeloid pathway produces DC3s and monocytes; DC3s have a lower requirement for IRF8 and expand in partial IRF8 deficiency. High-dimensional flow cytometry, in vitro differentiation, allelic series of human IRF8 deficiency patients Immunity High 32735845
2022 FTO (m6A demethylase) directly binds m6A sites in the 3'UTR of IRF8 mRNA and induces its degradation; FTO inhibition restores IRF8 expression and suppresses T-ALL by inhibiting PI3K/AKT signaling. m6A sequencing, FTO knockdown/overexpression, IRF8 mRNA stability assay, in vivo T-ALL mouse model Advanced science Medium 36478193
2022 The lupus risk variant rs2280381 modulates PU.1 binding at an IRF8 enhancer that spatially contacts the IRF8 promoter; the enhancer RNA AC092723.1 recruits TET1 to the IRF8 promoter to regulate IRF8 expression through DNA demethylation. CRISPR activation, 3D chromatin interaction assay, TET1 ChIP, DNA methylation analysis, allele-specific enhancer RNA measurement Nature communications Medium 35388006
2016 Biallelic IRF8 mutations cause familial NK cell deficiency with impaired terminal maturation (paucity of CD56dim NK cells, increase in CD56bright cells) in an NK-cell-intrinsic manner, with dysregulation of multiple genes controlling maturation. Patient genetic analysis, Irf8−/− mouse NK phenotyping, bone marrow chimeras, gene expression profiling of NK developmental subsets The Journal of clinical investigation High 27893462
2020 IRF8 suppresses inflammasome activation in cDC1s by limiting expression of inflammasome-associated genes; reduced IRF8 in cDC1s leads to aberrant NLRP3 inflammasome activation and impaired CD8 T cell priming. Irf8 conditional KO in cDC1s, inflammasome assays, T cell priming assays Cell reports Medium 32375053
2018 mTOR controls monocyte/macrophage development at early stages through the STAT5-IRF8-CD115 pathway: mTOR deficiency causes overactivated STAT5 that downregulates IRF8, leading to decreased CD115 (M-CSFR) expression at transcriptional and translational levels. mTOR-deficient mice, mixed chimeras, STAT5 activation analysis, IRF8 protein measurement, CD115 transcriptional analysis Blood Medium 29463562

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 IRF8 mutations and human dendritic-cell immunodeficiency. The New England journal of medicine 468 21524210
2002 ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. The Journal of experimental medicine 336 12461077
2013 Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. The Journal of clinical investigation 286 24091328
2016 IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively. Immunity 272 27637148
2002 Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells. Blood 252 12393690
2013 Essential role of the IRF8-KLF4 transcription factor cascade in murine monocyte differentiation. Blood 208 23319570
2016 The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation. The Journal of experimental medicine 200 27001747
2020 Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans. Immunity 199 32735845
2018 Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance. Nature communications 190 29593283
1993 The genomic structure of the murine ICSBP gene reveals the presence of the gamma interferon-responsive element, to which an ISGF3 alpha subunit (or similar) molecule binds. Molecular and cellular biology 184 8321202
1998 Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. Blood 171 9414265
2002 ICSBP/IRF-8: its regulatory roles in the development of myeloid cells. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 163 11846985
2022 Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer. Immunity 155 36288724
2000 An IFN-gamma-inducible transcription factor, IFN consensus sequence binding protein (ICSBP), stimulates IL-12 p40 expression in macrophages. Journal of immunology (Baltimore, Md. : 1950) 149 10861061
2019 Cryptic activation of an Irf8 enhancer governs cDC1 fate specification. Nature immunology 148 31406378
2007 An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature 147 17687331
2007 The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 139 18055870
2015 Differential requirement for irf8 in formation of embryonic and adult macrophages in zebrafish. PloS one 123 25615614
2014 The transcription factor IRF8 activates integrin-mediated TGF-β signaling and promotes neuroinflammation. Immunity 122 24485804
2014 The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation. The Journal of experimental medicine 122 25288399
2008 IRF8 regulates B-cell lineage specification, commitment, and differentiation. Blood 120 18799728
2016 IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis. Immunity 118 27067057
2005 Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood 110 15947094
2018 Transcription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response. Immunity 105 29858012
2015 Regulation of bifurcating B cell trajectories by mutual antagonism between transcription factors IRF4 and IRF8. Nature immunology 105 26437243
2009 IRF8 regulates myeloid and B lymphoid lineage diversification. Immunologic research 104 18806934
2015 Regulation of myelopoiesis by the transcription factor IRF8. International journal of hematology 101 25749660
1995 Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors. The Journal of biological chemistry 99 7768900
2019 An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development. Nature immunology 95 31406377
2020 Role of IRF8 in immune cells functions, protection against infections, and susceptibility to inflammatory diseases. Human genetics 89 32232558
2016 Biallelic mutations in IRF8 impair human NK cell maturation and function. The Journal of clinical investigation 87 27893462
2003 ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 85 14615368
2003 Activation of the murine interleukin-12 p40 promoter by functional interactions between NFAT and ICSBP. The Journal of biological chemistry 82 12876285
2002 IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages. FEBS letters 69 12417340
2018 Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition. Protein & cell 66 30484118
2015 IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes. Nature communications 66 25775030
2002 ICSBP/IRF-8 transactivation: a tale of protein-protein interaction. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 66 11846986
2020 High Amount of Transcription Factor IRF8 Engages AP1-IRF Composite Elements in Enhancers to Direct Type 1 Conventional Dendritic Cell Identity. Immunity 64 32795402
2011 IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia. Cancer research 60 21487040
2017 Modelling IRF8 Deficient Human Hematopoiesis and Dendritic Cell Development with Engineered iPS Cells. Stem cells (Dayton, Ohio) 56 28090699
2002 Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion. The EMBO journal 56 11823414
2003 ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells. Blood 53 12933588
2021 A RUNX-CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes. Nature immunology 52 33603226
2021 ZMYND8-regulated IRF8 transcription axis is an acute myeloid leukemia dependency. Molecular cell 52 34358447
2016 PU.1 cooperates with IRF4 and IRF8 to suppress pre-B-cell leukemia. Leukemia 52 26932576
2020 Suppression of Inflammasome Activation by IRF8 and IRF4 in cDCs Is Critical for T Cell Priming. Cell reports 50 32375053
2022 IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage. Immunity 49 35830859
2020 IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish. Frontiers in immunology 46 32373114
2019 Epigenetic control of early dendritic cell lineage specification by the transcription factor IRF8 in mice. Blood 46 30796024
2019 Leukocyte-specific siRNA delivery revealing IRF8 as a potential anti-inflammatory target. Journal of controlled release : official journal of the Controlled Release Society 46 31634546
2018 Transcription Factor IRF8 Governs Enhancer Landscape Dynamics in Mononuclear Phagocyte Progenitors. Cell reports 46 29514092
2013 Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis. Genes and immunity 45 23965942
2013 Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance. The Journal of experimental medicine 45 24101380
2022 Transcription-independent regulation of STING activation and innate immune responses by IRF8 in monocytes. Nature communications 44 35973990
2018 mTOR masters monocyte development in bone marrow by decreasing the inhibition of STAT5 on IRF8. Blood 44 29463562
2014 IRF4 and IRF8: Governing the virtues of B Lymphocytes. Frontiers in biology 44 25506356
2013 A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma. Blood 44 23775715
2010 Interferon consensus sequence binding protein (ICSBP) decreases beta-catenin activity in myeloid cells by repressing GAS2 transcription. Molecular and cellular biology 44 20679491
2008 Constitutive activation of SHP2 in mice cooperates with ICSBP deficiency to accelerate progression to acute myeloid leukemia. The Journal of clinical investigation 44 18246201
2020 CD163 expression defines specific, IRF8-dependent, immune-modulatory macrophages in the bone marrow. The Journal of allergy and clinical immunology 43 32199911
2015 Characterization and expression analyses of five interferon regulatory factor transcripts (Irf4a, Irf4b, Irf7, Irf8, Irf10) in Atlantic cod (Gadus morhua). Fish & shellfish immunology 43 25731920
2022 IRF8: Mechanism of Action and Health Implications. Cells 42 36078039
1994 IFN consensus sequence binding protein (ICSBP) is a conditional repressor of IFN inducible promoters. International immunology 42 7526889
2015 Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia. Journal of pharmacological sciences 41 26318672
2012 IRF-8 controls melanoma progression by regulating the cross talk between cancer and immune cells within the tumor microenvironment. Neoplasia (New York, N.Y.) 41 23308054
2007 Icsbp1/IRF-8 is required for innate and adaptive immune responses against intracellular pathogens. Journal of immunology (Baltimore, Md. : 1950) 41 17675508
2015 Transcription factor IRF8 controls Th1-like regulatory T-cell function. Cellular & molecular immunology 40 26166768
2008 IFN consensus sequence binding protein (Icsbp) is critical for eosinophil development. Journal of immunology (Baltimore, Md. : 1950) 37 18802108
2008 Epigenetic silencing of the interferon regulatory factor ICSBP/IRF8 in human multiple myeloma. Experimental hematology 35 18922617
2018 Deletion of IRF8 (Interferon Regulatory Factor 8)-Dependent Dendritic Cells Abrogates Proatherogenic Adaptive Immunity. Circulation research 33 29436389
2019 Cooperation of PU.1 With IRF8 and NFATc1 Defines Chromatin Landscapes During RANKL-Induced Osteoclastogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 30721543
2012 miR-22 controls Irf8 mRNA abundance and murine dendritic cell development. PloS one 32 23251709
2022 Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery. Nature communications 31 35388006
2018 T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation. Journal of autoimmunity 31 30241692
2013 Genetic determinants of susceptibility to Mycobacterial infections: IRF8, a new kid on the block. Advances in experimental medicine and biology 31 23468103
2013 Batf3 and Id2 have a synergistic effect on Irf8-directed classical CD8α+ dendritic cell development. Journal of immunology (Baltimore, Md. : 1950) 30 24227775
2003 Nramp1-mediated innate resistance to intraphagosomal pathogens is regulated by IRF-8, PU.1, and Miz-1. The Journal of biological chemistry 30 12904288
2020 IRF8 Regulates Gram-Negative Bacteria-Mediated NLRP3 Inflammasome Activation and Cell Death. Journal of immunology (Baltimore, Md. : 1950) 29 32205422
2019 Inactivating Mutation in IRF8 Promotes Osteoclast Transcriptional Programs and Increases Susceptibility to Tooth Root Resorption. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 30840779
2021 Brd4 regulates NLRC4 inflammasome activation by facilitating IRF8-mediated transcription of Naips. The Journal of cell biology 28 33535228
2022 IL-10 inhibits osteoclast differentiation and osteolysis through MEG3/IRF8 pathway. Cellular signalling 27 35525407
2009 Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments. Immunologic research 27 18663414
2021 Downregulated IRF8 in Monocytes and Macrophages of Patients with Systemic Sclerosis May Aggravate the Fibrotic Phenotype. The Journal of investigative dermatology 26 33705797
2017 USP4 interacts and positively regulates IRF8 function via K48-linked deubiquitination in regulatory T cells. FEBS letters 26 28477415
1999 Interferon-gamma signaling in human retinal pigment epithelial cells mediated by STAT1, ICSBP, and IRF-1 transcription factors. Investigative ophthalmology & visual science 26 10102295
2024 IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs. Nature immunology 25 39313544
2014 Constitutive IRF8 expression inhibits AML by activation of repressed immune response signaling. Leukemia 25 24957708
2011 Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor shedding, and induction of IRF8. Annals of the New York Academy of Sciences 25 22082370
2009 ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the CCL6 and CCL9 chemokines. Blood 25 19171873
2013 IRF5, IRF8, and IRF7 in human pDCs - the good, the bad, and the insignificant? European journal of immunology 24 23828296
2010 The combination of gene perturbation assay and ChIP-chip reveals functional direct target genes for IRF8 in THP-1 cells. Molecular immunology 24 20573402
2021 IRF-8/miR-451a regulates M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development. Cell death discovery 23 34282122
2016 Two Genetic Variations in the IRF8 region are associated with Behçet's disease in Han Chinese. Scientific reports 23 26794091
2022 Silencing of IRF8 Mediated by m6A Modification Promotes the Progression of T-Cell Acute Lymphoblastic Leukemia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 22 36478193
2021 PU.1 and IRF8 Modulate Activation of NLRP3 Inflammasome via Regulating Its Expression in Human Macrophages. Frontiers in immunology 22 33897697
2015 Dual Function of the IRF8 Transcription Factor in Autoimmune Uveitis: Loss of IRF8 in T Cells Exacerbates Uveitis, Whereas Irf8 Deletion in the Retina Confers Protection. Journal of immunology (Baltimore, Md. : 1950) 22 26163590
2008 Decreased IRF8 expression found in aging hematopoietic progenitor/stem cells. Leukemia 22 18596738
2006 ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells. Blood 22 16569763
2022 Host Cells Actively Resist Porcine Reproductive and Respiratory Syndrome Virus Infection via the IRF8-MicroRNA-10a-SRP14 Regulatory Pathway. Journal of virology 21 35293774
2021 IRF8 Is an AML-Specific Susceptibility Factor That Regulates Signaling Pathways and Proliferation of AML Cells. Cancers 21 33673123