Affinage

IL1RAP

Interleukin-1 receptor accessory protein · UniProt Q9NPH3

Length
570 aa
Mass
65.4 kDa
Annotated
2026-06-10
79 papers in source corpus 24 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL1RAP (IL-1RAcP) is an essential shared co-receptor that assembles ligand-induced heterotrimeric signaling complexes for the IL-1 cytokine family, converting cytokine engagement of primary receptors into intracellular activation of NF-κB and MAPK pathways (PMID:9065432, PMID:31427775). Reconstitution in non-responder cells established IL-1RAcP as the indispensable second chain that restores IL-1-driven IRAK activation, SAPK/JNK signaling, and NF-κB nuclear translocation (PMID:9065432), and a single blocking antibody against IL1RAP simultaneously neutralizes signaling by IL-1α, IL-1β, IL-33, and the IL-36 cytokines, confirming its role as the common co-receptor across the IL-1R1, ST2/IL-1RL1, and IL-36R primary receptors (PMID:31427775, PMID:14734551). Within the liganded complex, IL-1RAcP nucleates a stable signaling module containing MyD88 and IRAK-4, with IRAK-4 the earliest phosphorylated component (PMID:17507369); structural work on the IL-1β/IL-1R1/IL-1RAcP and IL-33/ST2/IL-1RAcP ternary complexes defines the architecture by which the co-receptor wraps onto the primary-receptor/cytokine assembly (PMID:19836339). Receptor abundance is restrained by MARCH8, an E3 ligase that interacts with IL1RAP and directs K48-linked polyubiquitination of Lys512 to drive its degradation and dampen NF-κB and MAPK output (PMID:22904187). Beyond canonical cytokine sensing, IL-1RAcP acts as a trans-synaptic adhesion molecule whose first Ig domain engages PTPδ (PTPRD) in a splice-insert-dependent manner to organize excitatory synapse differentiation, a function required for normal synaptic transmission in dentate gyrus granule cells (PMID:25908590, PMID:40360498). In cancer, IL1RAP physically associates with the receptor tyrosine kinases FLT3 and c-KIT in AML to sustain proliferative signaling (PMID:29773641) and with the system Xc- antiporter subunit SLC3A2 in Ewing sarcoma, where it enhances cystine uptake, induces the transsulfuration enzyme CTH, and suppresses anoikis (PMID:34021002). Loss-of-function and biallelic IL1RAP variants in patients link the gene to schizophrenia, via impaired neurite growth and signaling (PMID:35181481), and to steroid-sensitive nephrotic syndrome, via defective IL-1β binding and reduced cytokine production (PMID:31954058). Isoform-specific splicing of IL1RAP further tunes pathway output and contributes to tau phosphorylation and immune evasion phenotypes (PMID:41353558, PMID:29429992).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1997 High

    Established that IL-1RAcP is not a passive accessory chain but an indispensable signaling component, resolving why IL-1RI alone cannot transduce IL-1.

    Evidence cDNA transfection into an IL-1 non-responder line with IRAK, SAPK/JNK, NF-κB, and mRNA-induction readouts

    PMID:9065432

    Open questions at the time
    • Did not define the stoichiometry or contact surfaces of the receptor complex
    • Did not address other IL-1 family ligands
  2. 2000 High

    Demonstrated an in vivo physiological requirement for IL-1RAcP in centrally driven neuroendocrine and immune responses to IL-1β.

    Evidence IL-1RAcP knockout mice with intracerebroventricular IL-1β and corticosterone, splenocyte, and IL-6 readouts

    PMID:11024543

    Open questions at the time
    • Did not distinguish which downstream pathway accounts for each phenotype
    • Did not address tissue-specific or isoform-specific contributions
  3. 2001 Low

    Proposed a structural model for how IL-1RAcP docks onto the IL-1β/IL-1RI assembly, beginning to explain ternary complex geometry.

    Evidence Homology modeling and docking validated with IL-1β peptides, blocking antibodies, and mutant IL-1β

    PMID:11418113

    Open questions at the time
    • Primarily computational with indirect experimental validation
    • No high-resolution structure of the full ternary complex
  4. 2004 High

    Extended IL-1RAcP's co-receptor role beyond IL-1 to the IL-36 cytokines (IL-1F6/F8/F9) signaling through IL-1Rrp2.

    Evidence Blocking antibodies and dominant-negative IL-1RAcP with NF-κB/MAPK and cytokine-secretion readouts

    PMID:14734551

    Open questions at the time
    • Did not resolve the structural basis of IL-36R/IL-1RAcP assembly
    • Did not test in vivo relevance
  5. 2007 High

    Defined the composition and kinetics of the endogenous IL-1RI signaling complex, identifying the stable IL-1RAcP/MyD88/IRAK-4 module and IRAK-4 as the earliest phosphorylated component.

    Evidence Immunoprecipitation of endogenous complex with tandem mass spectrometry and in vitro phosphorylation

    PMID:17507369

    Open questions at the time
    • Did not establish direct contacts between IL-1RAcP and MyD88/IRAK-4
    • Kinetics defined in one cell context
  6. 2009 High

    Provided a unifying structural model of IL-1 family ternary signaling by characterizing both the IL-33/ST2/IL-1RAcP and IL-1β/IL-1R1/IL-1RAcP complexes.

    Evidence NMR structure of IL-33 and SAXS of the ternary complexes with biochemical binding assays

    PMID:19836339

    Open questions at the time
    • Low-resolution envelope rather than atomic complex structure
    • Did not map signaling-critical residues
  7. 2012 High

    Identified a negative-regulatory mechanism controlling IL-1RAcP abundance through MARCH8-mediated K48 ubiquitination of Lys512.

    Evidence Reciprocal Co-IP, K48-linkage ubiquitination assay, Lys512 mutagenesis, and overexpression/knockdown with NF-κB reporter

    PMID:22904187

    Open questions at the time
    • Did not establish the physiological trigger for MARCH8 engagement
    • In vivo relevance not tested
  8. 2013 Medium

    Showed that exon-9 skipping generates a soluble decoy IL-1RAcP that inhibits IL-1 signaling, providing a splicing-based therapeutic strategy.

    Evidence AON-mediated exon skipping in vitro and in mouse liver with RT-PCR, Western blot, and signaling inhibition

    PMID:23340324

    Open questions at the time
    • Did not demonstrate disease efficacy in vivo
    • Single lab
  9. 2015 High

    Revealed a non-cytokine function: IL-1RAcP acts as a trans-synaptic adhesion partner of PTPδ, defining the structural basis of splice-insert-dependent synaptic organization.

    Evidence X-ray crystallography of PTPδ/IL-1RAcP and PTPδ/IL1RAPL1 complexes with splice-insert domain mapping

    PMID:25908590

    Open questions at the time
    • Did not establish in vivo synaptic phenotype at the time
    • Did not link to downstream signaling
  10. 2016 Medium

    Implicated IL1RAP in leukemic stem cell biology by showing it is required for IL-1-driven NF-κB activation and proliferation in primitive CML cells and is therapeutically targetable.

    Evidence NF-κB and proliferation assays with IL1RAP-blocking antibodies and CML xenograft ADCC model

    PMID:27621309

    Open questions at the time
    • Did not define IL1RAP partners beyond IL-1 signaling in CML
    • Single lab
  11. 2018 Medium

    Expanded IL1RAP's oncogenic role by showing physical interaction with FLT3 and c-KIT in AML, coupling it to receptor tyrosine kinase signaling.

    Evidence Co-IP of IL1RAP-FLT3/c-KIT, RNAi, genetic deletion, and antibody treatment in AML models

    PMID:29773641

    Open questions at the time
    • Co-IP did not establish direct versus indirect binding
    • Mechanism of kinase activation by IL1RAP not resolved
  12. 2018 Medium

    Linked IL1RAP splicing to immune evasion, showing SRSF10-driven membrane isoform production activates NF-κB and CD47 to inhibit phagocytosis.

    Evidence Splicing assay, isoform RT-PCR, NF-κB reporter, CD47 analysis, and macrophage phagocytosis assay with SRSF10 manipulation

    PMID:29429992

    Open questions at the time
    • Did not define how membrane isoform selectively drives CD47
    • Single lab
  13. 2019 High

    Confirmed IL1RAP as the single shared co-receptor for IL-1, IL-33, and IL-36 signaling in vivo through a pan-blocking antibody.

    Evidence Blocking monoclonal antibody across in vitro signaling and three in vivo disease models

    PMID:31427775

    Open questions at the time
    • Did not resolve receptor-specific recruitment mechanisms
    • Did not address non-cytokine functions
  14. 2020 Medium

    Connected IL1RAP to a Mendelian disease by showing biallelic variants impair IL-1R complex function in steroid-sensitive nephrotic syndrome.

    Evidence Whole-exome sequencing, patient PBMC cytokine assays, and reconstitution of IL-1R with variant IL1RAP plus binding assays

    PMID:31954058

    Open questions at the time
    • Small patient cohort
    • Causal mechanism linking signaling defect to renal phenotype not established
  15. 2021 Medium

    Identified Arg286 as a key interaction residue for ternary complex formation and a druggable target for IL-1 signaling inhibition.

    Evidence Molecular modeling, pull-down complex-formation assay with peptide inhibitors, and anti-IL-1RAcP mAb in a mouse OA model

    PMID:33614593

    Open questions at the time
    • Key residue identification relied on modeling
    • In vivo efficacy limited to one disease model
  16. 2021 High

    Revealed a metabolic function of IL1RAP via SLC3A2 binding that supports cysteine supply, redox homeostasis, and anoikis resistance in Ewing sarcoma.

    Evidence Proteomic screen, Co-IP with SLC3A2, cystine uptake/glutathione assays, CTH analysis, anoikis and metastasis models

    PMID:34021002

    Open questions at the time
    • Direct versus complex-mediated SLC3A2 interaction not fully resolved
    • Generalizability beyond Ewing sarcoma untested
  17. 2021 Medium

    Showed IL1RAP enables AML cells to remodel the marrow niche by driving an IL-1β/p38/NF-κB pro-inflammatory secretome that suppresses normal HSPCs.

    Evidence IL1RAP knockdown, colony assays, secretome profiling, MSC co-culture, and Anakinra rescue

    PMID:33121233

    Open questions at the time
    • Did not separate IL1RAP secretome effects from RTK signaling
    • Single lab
  18. 2022 Medium

    Linked IL1RAP loss-of-function to schizophrenia through impaired neurite growth and IL-1 signaling.

    Evidence Whole-exome sequencing, shRNA knockdown, WT versus R442* rescue, JNK and NF-κB readouts in cortical neurons

    PMID:35181481

    Open questions at the time
    • Single patient variant
    • Causal contribution to disease at population level not established
  19. 2022 Medium

    Established that IL1RAP blockade overcomes IL-1-driven chemoresistance by disrupting tumor-stroma IL-1α/IL-1β crosstalk.

    Evidence NSCLC PDX and MC38 models with cytokine measurement and anti-IL1RAP versus anti-IL-1β comparison

    PMID:36036818

    Open questions at the time
    • Did not define which stromal cell types dominate the response
    • Single lab
  20. 2024 Medium

    Showed IL1RAP blockade reprograms the PDAC microenvironment by blocking CAF-derived chemokine secretion and myeloid recruitment.

    Evidence CAF/PDAC co-transplantation model, RNA-seq, migration assays, and nadunolimab treatment

    PMID:39694705

    Open questions at the time
    • Antitumor effect required CAF co-transplant, limiting interpretation in native tumors
    • Single lab
  21. 2025 High

    Provided genetic epistasis demonstrating that PTPδ-meB regulates excitatory synapses in dentate gyrus granule cells in an IL1RAP-dependent manner.

    Evidence Ptprd-meB and IL1RAP mutant mice with electrophysiology and postsynaptic density proteomics

    PMID:40360498

    Open questions at the time
    • Did not resolve the downstream signaling from the synaptic adhesion complex
    • Limited to one neuronal population
  22. 2025 Medium

    Demonstrated isoform-specific roles of IL-1RAcP in tau regulation during systemic inflammation.

    Evidence Global and neuron-specific Il1rap knockout mice in an LPS model with phospho-tau and total-tau readouts

    PMID:41353558

    Open questions at the time
    • Mechanism linking IL-1RAcP isoforms to tau kinases unresolved
    • Single lab
  23. 2025 Medium

    Implicated IL1RAP as a driver of inflammation-dependent clonal hematopoiesis expansion in Tet2-mutant clones.

    Evidence IL1RAP knockdown in vivo in a particulate-matter-exposed murine Tet2 CH model with flow cytometry

    PMID:41031953

    Open questions at the time
    • Did not define the signaling pathway driving clonal advantage
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IL1RAP coordinates its distinct functions — cytokine co-receptor, RTK-associated oncogenic scaffold, metabolic SLC3A2 partner, and trans-synaptic adhesion molecule — within a single cell, and which isoforms and post-translational states partition these roles, remains unresolved.
  • No integrated model reconciling cytokine signaling versus RTK and metabolic functions
  • Isoform-specific structural and signaling determinants incompletely mapped
  • Atomic structures of IL1RAP in non-cytokine complexes (FLT3, c-KIT, SLC3A2) lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 2
Partners
FLT3IL1R1IRAK4KITMARCH8MYD88PTPRDSLC3A2
Complex memberships
IL-1β/IL-1R1/IL-1RAcP ternary complexIL-33/ST2/IL-1RAcP complexIL-36γ/IL-36R/IL-1RAcP complexPTPδ/IL-1RAcP trans-synaptic complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 IL-1RAcP (IL1RAP) is an indispensable co-receptor component of the IL-1 receptor signaling complex: transfection of IL-1RAcP into IL-1 non-responder cells (EL-4 D6/76, which express IL-1RI but lack IL-1RAcP) was sufficient to restore IL-1-induced activation of IRAK, stress-activated protein kinases, NF-κB and IL-1 NF nuclear translocation, and IL-2 mRNA induction. cDNA transfection into IL-1 non-responder cell line, IRAK kinase assay, SAPK/JNK activation assay, nuclear translocation assay, mRNA induction The Journal of biological chemistry High 9065432
2004 IL-1F6, IL-1F8, and IL-1F9 (novel IL-1 family cytokines) signal through the orphan receptor IL-1Rrp2 AND require IL-1RAcP as a co-receptor: antibodies against IL-1RAcP and transfection of cytoplasmically-deleted (dominant-negative) IL-1RAcP blocked NF-κB activation by all three cytokines; full signaling activated NF-κB, JNK, ERK1/2, IL-8 promoter, and IL-6 secretion. Blocking antibodies against IL-1RAcP, dominant-negative cytoplasmic deletion transfection, NF-κB reporter assay, MAPK activation assay, cytokine secretion The Journal of biological chemistry High 14734551
2000 IL-1RAcP is required in vivo for centrally mediated neuroendocrine and immune responses to IL-1β: IL-1RAcP knockout mice fail to show IL-1β-induced plasma corticosterone elevation, splenocyte proliferation depression, or increases in plasma/brain IL-6 following intracerebroventricular IL-1β injection. IL-1RAcP knockout mice, intracerebroventricular injection, corticosterone ELISA, splenocyte proliferation assay, IL-6 measurement Journal of neuroimmunology High 11024543
2007 The endogenous IL-1RI signaling complex formed after IL-1 binding stably contains IL-1RAcP, MyD88, and IRAK-4 (p60); IRAK-4 is the earliest phosphorylated component. IRAK-1 (p90) is only transiently associated. IL-1RAcP, MyD88, and IRAK-4 associate with the liganded receptor within 15 seconds and remain stably associated. Immunoprecipitation of endogenous IL-1RI complex followed by tandem mass spectrometry, in vitro phosphorylation assay, SDS-PAGE mobility shift Molecular & cellular proteomics : MCP High 17507369
2001 Computational/experimental modeling of the IL-1RAcP interaction with the IL-1β/IL-1R(I) complex supports a 'BACK' model in which IL-1RAcP contacts the back of IL-1RI wrapped around IL-1β; this was validated by IL-1β peptide/antibody experiments and mutated IL-1β proteins. Homology modeling, computational docking, validation with IL-1β peptides, antibody blocking experiments, and mutated IL-1β proteins FEBS letters Low 11418113
2009 IL-33 forms a heterotrimeric signaling complex with its primary receptor ST2 and the coreceptor IL-1RAcP; solution structure of IL-33 was solved by NMR and SAXS was used to characterize the IL-33/ST2/IL-1RAcP and IL-1β/IL-1R1/IL-1RAcP ternary complexes, proposing a general model of IL-1 family ternary signaling complex architecture. NMR structure determination, small-angle X-ray scattering (SAXS), biochemical binding assays Structure (London, England : 1993) High 19836339
2012 The E3 ubiquitin ligase MARCH8 negatively regulates IL-1β-induced NF-κB signaling by physically interacting with IL1RAP and targeting its Lys512 for K48-linked polyubiquitination, leading to IL1RAP degradation. MARCH8 overexpression inhibits IL-1β-induced NF-κB and MAPK activation; MARCH8 knockdown has the opposite effect. Co-immunoprecipitation, ubiquitination assay with K48-linkage-specific analysis, site-directed mutagenesis (Lys512), overexpression and knockdown, NF-κB reporter assay Proceedings of the National Academy of Sciences of the United States of America High 22904187
2013 Antisense oligonucleotide (AON)-mediated skipping of exon 9 of IL-1RAcP (which encodes the transmembrane domain) produces a novel soluble, secreted form of IL-1RAcP (Δ9IL-1RAcP) that substantially inhibits IL-1 signaling in vitro; a single 10 mg/kg AON injection induced 90% exon skipping in mouse liver for at least 5 days. AON-mediated exon skipping in vitro and in vivo, RT-PCR, Western blot for secreted protein, IL-1 signaling inhibition assay Molecular therapy. Nucleic acids Medium 23340324
2015 Crystal structures of PTPδ in complex with IL-1RAcP and IL1RAPL1 reveal that the first Ig domain of IL-1RAcP binds to the second and third Ig domains of PTPδ in a splice-insert-dependent manner; the second splice insert of PTPδ acts as an adjustable linker positioning Ig2/Ig3 for simultaneous interaction with IL-1RAcP or IL1RAPL1 Ig1. This trans-synaptic interaction mediates synapse differentiation. X-ray crystallography of PTPδ/IL-1RAcP and PTPδ/IL1RAPL1 complexes, structure-function analysis of splice inserts Nature communications High 25908590
2018 IL1RAP physically interacts with FLT3 and c-KIT receptor tyrosine kinases in AML cells, mediating signaling and pro-proliferative effects through these receptors in addition to its known role in IL-1 receptor signaling. Targeting IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo without perturbing healthy hematopoietic function. Co-immunoprecipitation demonstrating IL1RAP-FLT3 and IL1RAP-c-KIT interaction, RNA interference, genetic deletion, antibody treatment, in vitro and in vivo AML models The Journal of experimental medicine Medium 29773641
2018 IL1RAP alternative splicing is regulated by the splicing factor SRSF10 (upregulated by HPV E6/E7 via E2F1): SRSF10 promotes use of an alternate terminator in IL1RAP exon 13 to increase production of the membrane form of IL1RAP (mIL1RAP). mIL1RAP activates NF-κB, which upregulates CD47 ('don't eat me' signal) to inhibit macrophage phagocytosis. RNA splicing assay, RT-PCR for isoform switching, NF-κB reporter, CD47 expression analysis, macrophage phagocytosis assay, SRSF10 knockdown/overexpression Oncogene Medium 29429992
2019 A single blocking monoclonal antibody against IL-1R3/IL1RAP simultaneously inhibits signaling by IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ in vitro and in vivo, confirming IL1RAP as the shared co-receptor for all three signaling pathways (IL-1R1, ST2/IL-1RL1, and IL-36R). Blocking monoclonal antibody in vitro signaling assays, in vivo mouse models (crystal-induced peritonitis, allergic airway inflammation, psoriasis) Nature immunology High 31427775
2021 IL1RAP binds the cell-surface system Xc- cystine/glutamate antiporter (SLC3A2) to enhance exogenous cystine uptake and replenish glutathione. Under cystine depletion, IL1RAP induces cystathionine gamma lyase (CTH) to activate the transsulfuration pathway for de novo cysteine synthesis, thereby maintaining redox homeostasis and suppressing anoikis in Ewing sarcoma cells. Proteomic screens, IL1RAP inactivation (loss-of-function), co-immunoprecipitation with SLC3A2, cystine uptake assay, glutathione measurement, CTH expression analysis, anoikis assay, metastasis models Cancer discovery High 34021002
2019 IL1RAP (IL1R3) is required for IL-1-induced NF-κB activation and proliferation in primitive CML cells (CD34+CD38-): antibodies blocking IL-1RAP signaling inhibit these effects. In vivo administration of IL1RAP antibodies in CML xenograft mice produced therapeutic effects mediated by effector cells (ADCC). NF-κB activation assay, proliferation assay, IL1RAP-blocking antibodies, CML xenograft mouse model, flow cytometry Blood Medium 27621309
2022 A nonsense mutation (c.1324C>T; R442*) in IL1RAP identified in schizophrenia patients is a loss-of-function mutation: lentiviral shRNA knockdown of IL1RAP suppressed axon and dendrite growth in mouse cortical neurons; this was rescued by wild-type but not R442* IL1RAP. Overexpression of R442* inhibited neuronal growth and IL-1β-induced JNK phosphorylation, and partially blocked NF-κB nuclear translocation in HePG2 cells. Whole-exome sequencing, lentiviral shRNA knockdown, wild-type rescue, mutant overexpression, JNK phosphorylation assay, NF-κB nuclear translocation assay, cortical neuron culture Neuroscience letters Medium 35181481
2020 Biallelic IL1RAP variants (p.I175T and p.R221H) in patients with steroid-sensitive nephrotic syndrome cause impaired IL-1R complex function: peripheral blood mononuclear cells from patients showed markedly lower cytokine production upon IL-1β stimulation; reconstitution of IL-1R with variant IL1RAP subunits showed impaired IL-1β binding and low reactivity. Whole-exome sequencing, cytokine production assay from patient PBMCs, reconstitution of IL-1R complex in hematopoietic cell line with variant IL1RAP, binding assay International immunology Medium 31954058
2021 Arg286 of IL-1RAcP is a key mediator of ternary IL-1β/IL-1R1/IL-1RAcP complex formation: molecular modeling identified Arg286 as a high-energy interaction mediator; inhibitory peptides based on the Arg286 region had an IC50 of 304 pM in a pull-down complex formation assay and reduced IL-1β signaling by 90% at 2 μM in cell models; anti-IL-1RAcP mAbs targeting Arg286 reduced inflammatory cell influx in a mouse OA model. Molecular modeling, pull-down complex formation assay, cell-based IL-1β signaling assay with peptide inhibitors, anti-IL-1RAcP monoclonal antibody in mouse OA model Frontiers in chemistry Medium 33614593
2021 IL1RAP knockdown in AML cells reduced colony-forming capacity; IL-1β stimulation of IL1RAP-expressing AML cells via p38 MAPK and NF-κB induced a pro-inflammatory secretome of chemokines that suppressed normal hematopoietic stem/progenitor cell function; blockade with the IL-1 receptor antagonist Anakinra reversed this effect. IL1RAP knockdown, colony formation assay, IL-1β stimulation, NF-κB/p38 pathway analysis, cytokine/chemokine secretome profiling, co-culture with mesenchymal stem cells, Anakinra rescue experiment Haematologica Medium 33121233
2019 Ginsenoside Rd suppresses IL-1β-induced inflammation in intervertebral disc chondrocytes by increasing IL1RAP ubiquitination mediated by the E3 ligase ITCH; Rd increased intracellular ITCH levels and the amount of ITCH attached to IL1RAP, blocking NF-κB stimulation. Immunoprecipitation, Western blot, PCR, bioinformatics analysis of E3 ligase candidates, CCK-8 viability assay, flow cytometry Brazilian journal of medical and biological research Low 31411316
2025 PTPδ-meB (mini-exon B of PTPδ/PTPRD) regulates excitatory synapses specifically in dentate gyrus granule cells in an IL1RAP-dependent manner: Ptprd-meB+/- mice showed decreased excitatory synaptic density and transmission in DG-GCs and reduced postsynaptic density levels of IL1RAP; IL1RAP-mutant mice showed the same decrease in excitatory synaptic transmission. Knock-in mutant mice (Ptprd-meB-/-), electrophysiology, proteomics of postsynaptic density, IL1RAP-mutant mouse phenotyping, behavioral analysis Nature communications High 40360498
2025 Global and neuron-specific IL-1RAcP isoform deficiency reduces hyperphosphorylated tau (pS202/AT8 and pT231/AT180) levels in LPS-induced systemic inflammation mouse model; neuron-specific IL-1RAcPb deficiency specifically increased total tau levels, indicating isoform-specific roles in tau regulation. Il1rap global and neuron-specific knockout mice, LPS-induced systemic inflammation model, immunohistochemistry/Western blot for phospho-tau epitopes ASN neuro Medium 41353558
2024 IL1RAP blockade in PDAC inhibits IL-1-induced chemokine secretion from cancer-associated fibroblasts (CAFs), reducing recruitment of neutrophils and monocytes; media conditioned by IL-1-stimulated CAFs maintained a neutrophil tissue-invasion phenotype that was reversed by nadunolimab; antitumor effects of nadunolimab required CAF co-transplantation. CAF/PDAC xenograft co-transplantation model, RNA sequencing, migration assay, neutrophil phenotype analysis, IL1RAP-blocking antibody (nadunolimab) Journal for immunotherapy of cancer Medium 39694705
2022 IL1RAP blockade reduces IL-1β-induced chemoresistance; chemotherapy induces IL-1α release from tumor cells and upregulates ICE (caspase-1) in tumor stroma, which processes IL-1β; IL-1α acts on stromal cells to further induce IL-1β secretion—effects disrupted by anti-IL1RAP antibody nadunolimab but not by anti-IL-1β antibody alone. NSCLC PDX model and syngeneic MC38 model, cytokine measurement, in vitro tumor cell line experiments, antibody blockade Cancer immunology, immunotherapy : CII Medium 36036818
2025 IL1RAP is overexpressed in Tet2-mutant clonal hematopoiesis clones; genetic knockdown of IL1RAP inhibited mutant clone growth in vivo in particulate matter-exposed mice, identifying IL1RAP as a driver of inflammation-dependent CH expansion. IL1RAP knockdown in vivo, murine CH model with Tet2 mutation, flow cytometry for clonal expansion Cancer discovery Medium 41031953
2025 Structural basis for IL-36R activation by IL-36γ involves low-affinity IL-36R binding followed by high-affinity IL-1RAcP recruitment; the IL-1RAcP shared receptor is recruited to the IL-36R complex with high affinity following cytokine engagement; spesolimab acts as an allosteric antagonist of IL-36R. Cryo-EM/X-ray crystallography of IL-36R/IL-36γ and IL-36R/IL-37 complexes, binding affinity measurements, functional signaling assays bioRxivpreprint Medium
2024 Ethanol drinking sex-dependently shifts mPFC IL-1RAcP isoform gene expression (brain-specific vs. peripheral isoform), which correlates with sex-dependent changes in IL-1β regulation of mPFC GABA synapses; this isoform shift is proposed to contribute to female mPFC resiliency and male susceptibility in AUD. Two-bottle choice ethanol drinking paradigm in C57BL/6J mice, mPFC IL-1RAcP isoform mRNA quantification, electrophysiology of GABA synapses bioRxivpreprint Low

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. The Journal of biological chemistry 346 14734551
1997 The interleukin-1 receptor accessory protein (IL-1RAcP) is essential for IL-1-induced activation of interleukin-1 receptor-associated kinase (IRAK) and stress-activated protein kinases (SAP kinases). The Journal of biological chemistry 257 9065432
2009 Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes. Structure (London, England : 1993) 171 19836339
2013 Selective killing of candidate AML stem cells by antibody targeting of IL1RAP. Blood 110 23479569
2015 GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP. Brain : a journal of neurology 109 26268530
2012 The E3 ubiquitin ligase MARCH8 negatively regulates IL-1β-induced NF-κB activation by targeting the IL1RAP coreceptor for ubiquitination and degradation. Proceedings of the National Academy of Sciences of the United States of America 103 22904187
2018 SRSF10-mediated IL1RAP alternative splicing regulates cervical cancer oncogenesis via mIL1RAP-NF-κB-CD47 axis. Oncogene 101 29429992
2015 Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America 98 26261316
2021 Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma. Cancer discovery 84 34021002
2016 IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models. Blood 81 27621309
2018 CML Hematopoietic Stem Cells Expressing IL1RAP Can Be Targeted by Chimeric Antigen Receptor-Engineered T Cells. Cancer research 75 30514753
2018 IL1RAP potentiates multiple oncogenic signaling pathways in AML. The Journal of experimental medicine 74 29773641
2019 IL-1R3 blockade broadly attenuates the functions of six members of the IL-1 family, revealing their contribution to models of disease. Nature immunology 71 31427775
2007 Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components. Molecular & cellular proteomics : MCP 63 17507369
2001 Model of interaction of the IL-1 receptor accessory protein IL-1RAcP with the IL-1beta/IL-1R(I) complex. FEBS letters 62 11418113
2015 Mechanisms of splicing-dependent trans-synaptic adhesion by PTPδ-IL1RAPL1/IL-1RAcP for synaptic differentiation. Nature communications 52 25908590
2018 Potential regulatory network in the PSG10P/miR-19a-3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis. Journal of cellular and molecular medicine 40 30370628
2022 Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia. Journal for immunotherapy of cancer 34 35803613
2023 RapaCaspase-9-based suicide gene applied to the safety of IL-1RAP CAR-T cells. Gene therapy 32 37173386
2022 IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma. Allergy 31 35986608
2021 Overcoming target epitope masking resistance that can occur on low-antigen-expresser AML blasts after IL-1RAP chimeric antigen receptor T cell therapy using the inducible caspase 9 suicide gene safety switch. Cancer gene therapy 30 33414517
2021 The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis. Haematologica 29 33121233
2014 IL1RAP as a surface marker for leukemia stem cells is related to clinical phase of chronic myeloid leukemia patients. International journal of clinical and experimental medicine 29 25663975
2000 Interleukin 1 receptor accessory protein (IL-1RAcP) is necessary for centrally mediated neuroendocrine and immune responses to IL-1beta. Journal of neuroimmunology 29 11024543
2024 Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis. Annals of the rheumatic diseases 26 38594058
2022 Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer. Journal of hematology & oncology 24 35606824
2022 IL-1RAP, a Key Therapeutic Target in Cancer. International journal of molecular sciences 24 36499246
2017 microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro. Molecular & cellular proteomics : MCP 22 29217619
2021 The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma. Technology in cancer research & treatment 19 33602046
2021 First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours. British journal of cancer 19 34903842
2013 Inhibition of IL-1 Signaling by Antisense Oligonucleotide-mediated Exon Skipping of IL-1 Receptor Accessory Protein (IL-1RAcP). Molecular therapy. Nucleic acids 18 23340324
2024 IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells. Journal of hematology & oncology 17 39143574
2023 CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans. Current research in translational medicine 17 36773434
2021 Circ_0037078 promotes trophoblast cell proliferation, migration, invasion and angiogenesis by miR-576-5p/IL1RAP axis. American journal of reproductive immunology (New York, N.Y. : 1989) 17 34724268
2023 Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies. Critical reviews in oncology/hematology 15 37981104
2022 Blockade of IL-1α and IL-1β signaling by the anti-IL1RAP antibody nadunolimab (CAN04) mediates synergistic anti-tumor efficacy with chemotherapy. Cancer immunology, immunotherapy : CII 15 36036818
2020 Associations of IL1RAP and IL1RL1 gene polymorphisms with obesity and inflammation mediators. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 15 31897507
2020 IL1RAP regulated by PRPRD promotes gliomas progression via inducing neuronal synapse development and neuron differentiation in vitro. Pathology, research and practice 14 32829106
2020 Structure-based Development of Human Interleukin-1β-Specific Antibody That Simultaneously Inhibits Binding to Both IL-1RI and IL-1RAcP. Journal of molecular biology 14 33359099
2024 Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment. Journal for immunotherapy of cancer 13 39694705
2021 Association of IL33, IL1RL1, IL1RAP Polymorphisms and Asthma in Chinese Han Children. Frontiers in cell and developmental biology 11 34977013
2020 Associations of IL6 rs1800795, BLK rs13277113, TIMP3 rs9621532, IL1RL1 rs1041973 and IL1RAP rs4624606 single gene polymorphisms with laryngeal squamous cell carcinoma. Gene 10 32330537
2019 Association of IL1RAP-related genetic variation with cerebrospinal fluid concentration of Alzheimer-associated tau protein. Scientific reports 10 30792413
2024 IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis. Circulation. Heart failure 8 39513273
2023 Characterisation of IL-1 family members in Sweet syndrome highlights the overexpression of IL-1β and IL-1R3 as possible therapeutic targets. Experimental dermatology 8 37724787
2024 Efficacy and Safety of the Anti-IL1RAP Antibody Nadunolimab (CAN04) in Combination with Gemcitabine and Nab-Paclitaxel in Patients with Advanced/Metastatic Pancreatic Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 7 39385434
2023 CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cell through regulating miR-942-5p/IL1RAP axis. American journal of reproductive immunology (New York, N.Y. : 1989) 7 37382169
2021 Identification and Targeting of Thomsen-Friedenreich and IL1RAP Antigens on Chronic Myeloid Leukemia Stem Cells Using Bi-Specific Antibodies. OncoTargets and therapy 6 33519209
2021 IL1RAP Pulls a Double Shift in the Cysteine Factory. Cancer discovery 6 34725089
2020 The Role of SNPs in IL1RL1 and IL1RAP Genes in Age-related Macular Degeneration Development and Treatment Efficacy. In vivo (Athens, Greece) 6 32871771
2013 The inhibitory function of Fc-ST2 depends on cell type; IL-1RAcP and ST2 are necessary but insufficient for IL-33 activity. Immunologic research 6 23435764
2022 Novel IL1RAP mutation associated with schizophrenia interferes with neuronal growth and related NF-κB signal pathways. Neuroscience letters 5 35181481
2021 Characterization and Validation of Arg286 Residue of IL-1RAcP as a Potential Drug Target for Osteoarthritis. Frontiers in chemistry 5 33614593
2019 Ginsenoside Rd inhibits IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 5 31411316
2016 Reconstitution of ST2 (IL-1R4) specific for IL-33 activity; no suppression by IL-1Ra though a common chain IL-1R3 (IL-1RAcP) shared with IL-1. Cytokine 5 27031441
2011 Engagement of IL-1 receptor accessory protein (IL-1RAcP) with the monoclonal antibody AY19 provides co-activating signals and prolongs the CD2-induced proliferation of peripheral blood lymphocytes. Immunology letters 5 21600927
2025 IL1RAP is an immunotherapeutic target for normal karyotype triple-mutated acute myeloid leukemia. Biomarker research 4 40229904
2025 IL1RAP Expression in Human Atherosclerosis: A Target of Novel Antibodies to Reduce Vascular Inflammation and Adhesion. Journal of the American Heart Association 4 40371594
2022 IL1RAP Knockdown in LPS-Stimulated Normal Human Astrocytes Suppresses LPS-Induced Reactive Astrogliosis and Promotes Neuronal Cell Proliferation. Neurochemical research 4 36502418
2020 Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome. International immunology 4 31954058
2020 Associations between IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, and HTRA1 rs11200638 gene polymorphisms and development of optic neuritis with or without multiple sclerosis. Ophthalmic genetics 4 32449403
2025 Elevated Clonal Hematopoiesis in 9/11 First Responders Has Distinct Age-related Patterns and Relies on IL1RAP for Clonal Expansion. Cancer discovery 3 41031953
2025 Alternatively spliced mini-exon B in PTPδ regulates excitatory synapses through cell-type-specific trans-synaptic PTPδ-IL1RAP interaction. Nature communications 2 40360498
2025 Global Deficiency of Alzheimer's Disease Risk Gene Il1rap Reduces Pathological Tau in a Mouse Model of Systemic Inflammation. ASN neuro 2 41353558
2024 ZO-1 and IL-1RAP Phosphorylation: Potential Role in Mediated Brain-Gut Axis Dysregulation in Irritable Bowel Syndrome-like Stressed Mice. International journal of medical sciences 2 39006851
2024 Circ_0003314 Combines with the miR-26b-5p/IL1RAP Axis to Inhibit HTR-8/SVneo Cell Proliferation, Migration, Invasion and Tube Formation and Promote Apoptosis. Applied biochemistry and biotechnology 2 39141177
2025 Safety, efficacy, and analysis of biomarkers in patients with advanced non-small cell lung cancer treated with the anti-IL1RAP antibody nadunolimab (CAN04) in combination with platinum doublet. Lung cancer (Amsterdam, Netherlands) 1 40680438
2025 MicroRNA-142 improves IL1RAP CAR-T cell activity in acute myeloid leukemia. Journal of hematology & oncology 1 41225489
2022 Bacterial production and biophysical characterization of a hard-to-fold scFv against myeloid leukemia cell surface marker, IL-1RAP. Molecular biology reports 1 36435922
2018 [Expressions and clinical significance of GAS1, IL-1RAP and PRF1 in patients with ALK positive anaplastic large cell lymphoma]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 1 29562445
2026 IL1RAP antibody-drug conjugates potently target primary and metastatic disease in multiple oncofusion-driven cancers. Cancer discovery 0 41973074
2026 Peripheral lncRNA-IL1RAP Dysregulation in Schizophrenia: A Multi-Omics Bridge Between Immunity and Diagnosis. Brain and behavior 0 41988836
2025 Association of IL-1RAcP rs16865597 gene polymorphism with susceptibility to essential hypertension: a case-control study in the Chinese Han population. BMC cardiovascular disorders 0 40075282
2024 IL1RAP Exacerbates Sepsis-Induced Pulmonary and Spleen Injury Through Regulating CD4+ T Lymphocyte Differentiation. Immunological investigations 0 38329477
2024 Circular RNA circMAN1A2 promotes ovarian cancer progression through the microRNA-135a-3p/IL1RAP/TAK1 pathway. PeerJ 0 38680890
2023 The survival rate of laryngeal squamous cell carcinoma: impact of IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532 single nucleotide polymorphisms. Discover oncology 0 36682035
2015 [Preparation and Assessment of IL1RAP Monoclonal Antibody]. Zhongguo shi yan xue ye xue za zhi 0 26314426
2015 [Cloning of VH and VL Gene of Human anti-IL1RAP McAb and Construction of Recombinant Chimeric Receptor]. Zhongguo shi yan xue ye xue za zhi 0 26524021
2013 [Construction of hybridoma cells with IL1RAP as a new marker for leukemia stem cells and detection of its monoclonal antibody]. Zhongguo shi yan xue ye xue za zhi 0 24370017

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