Affinage

IL1R1

Interleukin-1 receptor type 1 · UniProt P14778

Audit flag: ungrounded claim
Length
569 aa
Mass
65.4 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL1R1 is the principal signaling receptor for IL-1, transducing inflammatory cues into NF-κB, MAPK, and PI3K-mTOR programs across diverse tissues to coordinate innate immunity, adaptive T cell licensing, and tissue remodeling (PMID:1531143, PMID:30093533). Signal transduction requires conserved cytoplasmic TIR-domain residues (Arg431, Lys515, Arg518, Phe513, Trp514, Tyr519, Pro521) homologous to Drosophila Toll, and the IL-1R-like cytoplasmic module pairs combinatorially with any accessory-protein-like (AcP-like) domain to activate NF-κB (PMID:1531143, PMID:10882729). Downstream, IL-1R1 nucleates a Myddosome in which MyD88 must oligomerize above a threshold of more than four molecules to sequentially recruit IRAK4 and IRAK1, with IRAK4 itself limiting MyD88 oligomer growth (PMID:33956941); receptor fate is further controlled by TRAF6, which ubiquitinates IL-1R1 to drive ectodomain shedding and gamma-secretase-mediated regulated intramembrane proteolysis (PMID:19232518), while TOM1 terminates signaling (PMID:31570577). Beyond canonical NF-κB output, IL-1R1 engages the TIR-domain adapter BCAP to activate PI3K-Akt-mTOR and drive pathogenic Th17 differentiation, and it licenses effector cytokine production by stabilizing cytokine transcripts and promoting STAT3/RelA occupancy at Il17a/f regulatory elements (PMID:30093533, PMID:30093607, PMID:30093408). IL-1R1 acts in a markedly cell-type- and compartment-specific manner: on non-hematopoietic and bystander cells it confers trans-protection and emergency myelopoiesis during infection (PMID:19414802, PMID:26034289, PMID:30068597), on dendritic cells it primes antiviral CD8 and CD4 responses (PMID:23314004, PMID:23460727), on endothelium and CNS microvasculature it controls leukocyte trafficking and CXCL12 expression (PMID:25200953, PMID:20854891), on intestinal epithelium it amplifies IL-22R-STAT3-driven antimicrobial peptide production (PMID:36976181), and it drives osteoclastogenic bone loss during osteomyelitis (PMID:30978245). In the nervous system, neuronal IL-1R1 is restricted to discrete glutamatergic and serotonergic populations that signal through non-canonical, non-NF-κB routes and uniquely express the IL-1RAcPb isoform (PMID:39563437). IL-1R1 is also an obligate mediator of celastrol's leptin-sensitizing antiobesity effects (PMID:30833749) and is exploited in tumor stroma, where IL1R1+ cancer-associated fibroblasts promote colorectal cancer growth and immunosuppression (PMID:37460545).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1990 Medium

    Established that IL-1 binding activity in different cell types is biochemically heterogeneous, distinguishing the T cell-type IL-1R1 from a separate monocyte receptor species and framing the question of which protein mediates signaling.

    Evidence Competitive binding, SDS-PAGE/Western, Northern blot, and cDNA sequencing in monocytes versus T cells

    PMID:2148319

    Open questions at the time
    • Did not identify the molecular identity of the 63-kDa monocyte receptor
    • Did not connect receptor heterogeneity to distinct downstream signaling
  2. 1992 High

    Defined the cytoplasmic residues required for IL-1R1 signal transduction and revealed homology to Drosophila Toll, establishing the TIR-domain basis of IL-1 signaling.

    Evidence Site-directed mutagenesis of cytoplasmic residues with IL-2 promoter reporter in T cells

    PMID:1531143

    Open questions at the time
    • Did not identify the adapter proteins recruited by these residues
    • Did not resolve receptor complex stoichiometry
  3. 1998 Medium

    Provided the biophysical architecture of the IL-1R1 ectodomain, confirming a three immunoglobulin-like domain organization.

    Evidence Differential scanning calorimetry, circular dichroism, and SEC on recombinant receptor

    PMID:9523304

    Open questions at the time
    • No ligand-bound structure
    • Did not address accessory protein engagement
  4. 2000 Medium

    Demonstrated modular complementarity of IL-1R-family signaling units, showing the IL-1R1 cytoplasmic domain pairs with any AcP-like domain to activate NF-κB.

    Evidence Chimeric receptor panel with NF-κB reporter assays in transfected cells

    PMID:10882729

    Open questions at the time
    • Did not define endogenous receptor-coreceptor pairing in vivo
    • Reporter-based readout only
  5. 2009 Medium

    Identified TRAF6-dependent ubiquitination as the trigger for regulated intramembrane proteolysis of IL-1R1, revealing a post-translational route to receptor turnover.

    Evidence Wild-type versus ligase-dead TRAF6 co-expression with ubiquitination, shedding, and gamma-secretase cleavage assays

    PMID:19232518

    Open questions at the time
    • Functional consequence of RIP for signaling output not resolved
    • Single-lab overexpression system
  6. 2009 High

    Established that IL-1R1 drives emergency hematopoiesis non-cell-autonomously, requiring receptor expression on radiation-resistant host cells for neutrophilia.

    Evidence IL-1R1 KO mice and radiation chimeras with in vitro HSC proliferation assays

    PMID:19414802

    Open questions at the time
    • Identity of the responding non-hematopoietic cell not specified
    • Downstream mediators of neutrophilia not defined
  7. 2018 High

    Defined a non-canonical IL-1R1 output via the TIR adapter BCAP that activates PI3K-Akt-mTOR to drive pathogenic Th17 differentiation, and showed IL-1R1 licenses effector cytokine production by stabilizing transcripts and directing STAT3/RelA to Il17a/f loci.

    Evidence T cell-conditional BCAP and IL-1R1 KO mice, mTOR inhibition, ChIP for STAT3/RelA, mRNA stability assays, EAE model

    PMID:30093408 PMID:30093533 PMID:30093607

    Open questions at the time
    • Relative contribution of BCAP versus MyD88 routes not quantified
    • How transcript stabilization is mechanistically linked to receptor signaling not fully resolved
  8. 2021 High

    Resolved the physical logic of Myddosome assembly, showing MyD88 must oligomerize beyond four molecules to recruit IRAK4 then IRAK1, with IRAK4 limiting oligomer size.

    Evidence Live-cell single-molecule imaging of Myddosome dynamics with IRAK4 knockout

    PMID:33956941

    Open questions at the time
    • How receptor clustering sets the oligomerization threshold not defined
    • Connection to specific downstream NF-κB amplitude not quantified
  9. 2019 Medium

    Identified TOM1 as a negative regulator terminating IL-1R1 signaling, linking signal termination to amyloid clearance and cognition.

    Evidence TOM1 knockdown and overexpression in mouse brain with IL-1β signaling and Alzheimer's model readouts

    PMID:31570577

    Open questions at the time
    • Molecular step at which TOM1 acts on the receptor complex unclear
    • Single-lab bidirectional manipulation
  10. 2019 High

    Established IL1R1 as an obligate mediator of celastrol's leptin-sensitizing antiobesity effects, connecting the receptor to hypothalamic metabolic control.

    Evidence Hypothalamic transcriptome time-series and IL1R1 global KO metabolic phenotyping

    PMID:30833749

    Open questions at the time
    • Cell type and downstream pathway mediating leptin sensitization not defined
    • Endogenous ligand driving the effect not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The basis for the divergence between canonical NF-κB signaling and the non-canonical, non-transcriptional neuronal IL-1R1 outputs employing the IL-1RAcPb isoform remains unresolved.
  • Effector pathway downstream of neuronal IL-1R1 undefined
  • Whether AcP-like modular pairing rules apply to IL-1RAcPb not tested
  • Structural basis of isoform-specific signaling unknown

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:0038024 cargo receptor activity 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 1
Partners
BCAPIL1RAPIRAK1IRAK4MYD88TOM1TRAF6
Complex memberships
Myddosome

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Site-directed mutagenesis of the cytoplasmic domain of human IL-1R1 identified six conserved amino acids (Arg431, Lys515, Arg518, Phe513, Trp514, Tyr519) and Pro521 as essential for IL-1-mediated signal transduction (activation of IL-2 promoter in T cells); nonconserved residues could be replaced without effect. The cytoplasmic domain shares 26% identity with Drosophila Toll, and the essential residues are conserved in Toll, indicating functional homology. Site-directed mutagenesis of cytoplasmic domain residues combined with IL-2 promoter reporter assay in T cells The Journal of biological chemistry High 1531143
1990 The monocyte IL-1R protein (63 kDa) is immunologically and biochemically distinct from the T cell-type IL-1R1 (80 kDa), despite monocytes expressing an mRNA identical in coding region to the T cell IL-1R1 mRNA; neither the large nor the small monocyte mRNA appears to encode the 63-kDa monocyte receptor, indicating it is the product of a separate nonhomologous mRNA. Competitive binding assays, SDS-PAGE/Western blot, Northern blot, cDNA sequencing, immunological cross-reactivity analysis The Journal of biological chemistry Medium 2148319
1998 Differential scanning calorimetry (DSC) of recombinant IL-1R1 revealed three cooperative melting transitions consistent with unfolding of three immunoglobulin-like domains; circular dichroism confirmed approximately 39% beta-sheet secondary structure. NaCl most strongly stabilized the protein by shifting the low-temperature transition to 53°C. Differential scanning calorimetry (DSC), circular dichroism (CD), size-exclusion chromatography (SEC), SDS-PAGE Pharmaceutical research Medium 9523304
2009 TRAF6 preferentially ubiquitinates IL-1R1 among TRAF family members, and TRAF6 ubiquitin ligase activity promotes IL-1R1 ectodomain shedding and subsequent gamma-secretase cleavage (regulated intramembrane proteolysis, RIP). TRAF6 mutants defective in ubiquitin ligase activity failed to induce IL-1R1 ubiquitination or RIP. Co-expression of wild-type and ubiquitin-ligase-dead TRAF6 mutants with IL-1R1; ubiquitination assays; ectodomain shedding assays; gamma-secretase cleavage assays Biochemical and biophysical research communications Medium 19232518
2021 IL-1R1 Myddosome signaling requires MyD88 oligomerization above a physical threshold: formation of stable oligomers of more than four MyD88 molecules triggers sequential recruitment of IRAK4 then IRAK1. IRAK4 knockout enhanced MyD88 oligomerization, indicating IRAK4 negatively controls MyD88 oligomer size and growth, acting as a brake on signaling. Live-cell single-molecule imaging assay for spatiotemporal Myddosome assembly dynamics; genetic knockout of IRAK4; quantitative analysis of MyD88 oligomer size vs. downstream recruitment The Journal of cell biology High 33956941
2018 BCAP (B cell adapter for PI3K) acts as a novel TIR-domain adapter downstream of IL-1R1 to link IL-1 signaling to PI3K-Akt-mTOR activation. T cell-intrinsic BCAP deficiency selectively impaired IL-1R1-induced mTOR activation and pathogenic Th17 cell differentiation; minimal mTOR inhibition phenocopied BCAP deficiency, establishing the IL-1R1→BCAP→PI3K→mTOR axis. Conditional T cell-specific BCAP knockout mice; IL-1R1 signaling assays (PI3K-Akt-mTOR phosphorylation); mTOR inhibition; EAE model; Th17 differentiation assays The Journal of experimental medicine High 30093533
2018 IL-1R1 signaling in T cells stabilizes effector cytokine transcripts to enable productive cytokine production by committed Th1, Th2, and Th17 memory cells; acute abrogation of IL-1R1 signaling in vivo reduced IL-17A production by intestinal Th17 cells, establishing IL-1 as a licensing signal for memory CD4 T cell effector function. IL-1R1-deficient T cell transfers; in vivo IL-1R1 blockade; cytokine mRNA stability assays; flow cytometric cytokine measurement Nature communications High 30093607
2018 IL-1R1 signaling promotes STAT3 binding to key cis-regulatory elements controlling IL-17 expression, and the IL-1-induced NF-κB factor RelA directly regulates Il17a/f loci in cooperation with STAT3. IL-1β also enhances STAT3 phosphorylation via NF-κB-mediated repression of SOCS3. ChIP-seq/ChIP assays for STAT3 and RelA at Il17a/f loci; NF-κB pathway inhibition; SOCS3 reporter assays; Th17 differentiation in vitro The Journal of biological chemistry High 30093408
2019 IL1R1 is required for celastrol's leptin-sensitizing and antiobesity effects: IL1R1-deficient mice are completely resistant to celastrol treatment of obesity, diabetes, and nonalcoholic steatohepatitis. This was identified through temporally resolved hypothalamic transcriptome analysis followed by genetic validation. Hypothalamic transcriptome time-series in celastrol-treated mice; IL1R1 global knockout mice; metabolic phenotyping (body weight, leptin sensitivity, glucose tolerance, liver histology) Nature medicine High 30833749
2019 TOM1 (Target of Myb1) functions as a negative regulator of IL-1R1 signaling; reducing TOM1 levels impaired IL-1β signaling termination, increased amyloid-beta, and impaired cognition, while enhancing TOM1 levels was therapeutic in an Alzheimer's disease mouse model. TOM1 knockdown and overexpression in mouse brain; IL-1β signaling assays; amyloid-beta measurement; cognitive behavioral tests; human AD hippocampal tissue analysis Proceedings of the National Academy of Sciences of the United States of America Medium 31570577
2009 IL-1R1 signaling on radiation-resistant host cells (non-hematopoietic compartment) is both necessary and sufficient for alum-induced hematopoietic stem cell (HSC) and multipotent progenitor proliferation and reactive neutrophilia; IL-1 drives increased HSC proliferation directly in vitro, but the in vivo neutrophilia requires IL-1R1 on non-hematopoietic cells. IL-1R1 knockout mice; radiation chimeras reconstituted with WT or IL-1R1-/- bone marrow; in vitro HSC proliferation assays with IL-1; flow cytometric analysis of progenitor compartments Journal of immunology High 19414802
2013 IL-1R1 signaling on dendritic cells, activated by IL-1 in trans from influenza-infected cells, is required and sufficient for priming of virus-specific CD8+ T cells during live influenza A virus infection, replacing the requirement for direct PRR (TLR7/RIG-I) signaling on DCs. IL-1R1-/- mice; TLR7-/- and RIG-I-/- mice; adoptive transfer of IL-1-activated DCs; antigen-specific CD8+ T cell priming assays Nature immunology High 23314004
2013 IL-1R1 signaling on dendritic cells within the CNS is critical for CD11c+ cell activation and CD4+ T cell reactivation during West Nile virus encephalitis; adoptive transfer of WT CD11c+ cells into WNV-infected IL-1R1-/- mice restored T cell functions and improved survival. IL-1R1-/- mice; adoptive transfer of CD11c-EYFP+ cells; ex vivo T cell functional assays; flow cytometric analysis of co-stimulatory molecule expression The Journal of experimental medicine High 23460727
2014 IL-1R1 signaling regulates CXCL12 expression at the CNS microvasculature during WNV infection; CNS-infiltrating IL-1β-producing macrophages are the primary IL-1β source, and IL-1β promotes CXCR4-mediated T cell adhesion to brain microvasculature endothelial cells in vitro. Absence of IL-1R1 signaling decreases microvasculature CXCL12 and upregulates parenchymal chemokines CCL2, CCL5, CXCL10. IL-1R1-/- mice; in vitro blood-brain barrier model; flow cytometry identifying IL-1β-producing cell types; chemokine expression analysis; CXCR4/CXCL12 adhesion assays Journal of immunology Medium 25200953
2010 Endothelial cell-specific knockdown of IL-1R1 attenuates EAE incidence, severity, and onset, and reduces VCAM-1 expression and CD45+/CD3+ leukocyte infiltration into the spinal cord, establishing endothelial IL-1R1 as a critical mediator of CNS inflammation in EAE. Transgenic mice with endothelial-specific IL-1R1 knockdown (eIL-1R1 kd); EAE induction; VCAM-1 immunostaining; flow cytometric analysis of CNS infiltrating leukocytes Brain, behavior, and immunity High 20854891
2018 IL-1R1 signaling is required for osteoclast-mediated bone loss during S. aureus osteomyelitis: IL-1R1 KO mice showed reduced osteoclast abundance on bone surfaces and reduced trabecular bone loss despite having impaired local bacterial control, establishing IL-1R1 as a driver of osteoclastogenesis and collateral bone damage during infection. IL-1R1-/- mice; murine osteomyelitis model; osteoclast quantification on bone surfaces; trabecular bone microCT; in vitro osteoclastogenesis assays with S. aureus PLoS pathogens High 30978245
2015 IL-1R1 signaling in bystander (uninfected) macrophages is required for production of IL-6, TNF, and IL-12 during Legionella pneumophila infection; infected cells produce IL-1α and IL-1β but are poor producers of these cytokines due to bacterial translation blockade, establishing a collaboration mechanism whereby IL-1 from infected cells activates IL-1R1 on bystander cells to bypass pathogen-mediated immune evasion. Reporter system distinguishing infected vs. uninfected cells; IL-1R1-/- mice; cytokine production measurement in sorted cell populations; in vivo pulmonary infection model Proceedings of the National Academy of Sciences of the United States of America High 26034289
2018 IL-1R1-mediated host resistance to M. tuberculosis does not operate cell-autonomously within infected phagocytes but requires trans-protection: IL-1R1 expression by non-infected hematopoietic or non-hematopoietic cells provides resistance signals to infected cells in trans. Competitive mixed bone marrow chimeras; IL-1R1 conditional mutant mice; single-cell analysis of bacterial growth in IL-1R1+ vs. IL-1R1- cells Journal of immunology High 30068597
2023 IEC-intrinsic IL-1R1 signaling enhances IL-22R-induced STAT3 phosphorylation in intestinal epithelial cells, leading to elevated antimicrobial peptide (AMP) production; IL-1R1 signaling also directly induces chemokine expression and reactive oxygen species genes in IECs, establishing a dual homeostatic (antimicrobial) and pathological (colitis-promoting) role. IEC-specific IL-1R1 conditional KO mice; Citrobacter rodentium infection; DSS colitis model; STAT3 phosphorylation assays; AMP gene expression The Journal of experimental medicine High 36976181
2021 The MyD88/IL-1R axis regulates PD-1 expression on tumor-associated macrophages by promoting NF-κBp65 recruitment to the Pdcd1 promoter, maintaining their immunosuppressive function and driving melanoma progression. MyD88-/- mice; myeloid-specific MyD88 deletion; ChIP assay for NF-κBp65 at Pdcd1 promoter; flow cytometric analysis of TAM PD-1 expression; murine melanoma model Cancer research Medium 33619117
2004 The 3' UTR of the membrane-bound IL-1R accessory protein (mIL-1RAcP) mRNA confers tissue-specific mRNA destabilization in hepatoma cells (half-life ~5 h) but not in kidney cells (half-life ~48 h), mediated by novel non-AU-rich elements acting independently; this regulates cellular responsiveness to IL-1 in a tissue-specific manner. mRNA turnover assays in HepG2 and 293 cell lines; luciferase reporter constructs with 3' UTR deletions Journal of immunology Medium 15528363
2024 Neuronal IL-1R1 (nIL-1R1) is expressed in discrete glutamatergic (somatosensory cortex, piriform cortex, dentate gyrus) and serotonergic (dorsal raphe) neuronal populations. High-dose IL-1β (i.c.v.) activates NFκB in IL-1R1+ non-neuronal cells but NOT in IL-1R1+ neurons. Dentate gyrus neurons exclusively express an alternatively spliced IL-1R accessory protein isoform (IL-1RAcPb), a known synaptic adhesion molecule. IL-1R1 expression in DG neurons downregulates synaptic function genes and select complement markers via non-autonomous transcriptional pathways. Novel genetic mouse line (Il1r1GR/GR) for IL-1R1 visualization; Vglut2-Cre-Il1r1r/r conditional mice; i.c.v. IL-1β injection; NFκB reporter imaging; spatial RNA sequencing; gene expression profiling Journal of neuroinflammation High 39563437
2024 IL-1R signaling in enteric glia, triggered by tumor-infiltrating monocytes, drives a reactive glial phenotype that promotes monocyte differentiation toward pro-tumorigenic SPP1+ tumor-associated macrophages via IL-6 release, establishing a bi-directional neuroimmune circuit in colorectal cancer. Single-cell and bulk RNA sequencing in murine models and patient samples; glial IL-1R signaling blockade experiments; co-culture systems; in vivo tumor models Nature communications Medium 39030280
2023 A pro-tumorigenic IL1R1+ subtype of cancer-associated fibroblasts drives colorectal cancer tumor growth and immunosuppression; fibroblast-specific IL1R1 knockout and IL-1Ra (anakinra) administration both reduced tumor growth in vivo and decreased intratumoral Th17 infiltration. Single-cell sequencing of patient CRC datasets; fibroblast-specific IL1R1 conditional knockout; anakinra treatment in vivo; 3D co-culture assays; flow cytometry of intratumoral immune cells Nature communications High 37460545
2000 Using chimeric receptor functional assays, the cytoplasmic domain of IL-1R1 was classified as 'IL-1R-like' and can cooperate with any 'AcP-like' cytoplasmic domain to signal through NF-κB; any IL-1R-like domain can pair with any AcP-like domain, establishing modular complementarity of IL-1R family signaling units. Chimeric receptor constructs (extracellular/TM domain of IL-1R1 or IL-1RAcP fused to cytoplasmic domains of all family members); NF-κB reporter co-expression assays in transfected cells The Journal of biological chemistry Medium 10882729
2016 GPER (G protein estrogen receptor) activation in cancer-associated fibroblasts triggers IL-1β production; this IL-1β induces IL1R1 expression in breast cancer cells via GPER signaling, generating a feedforward loop that upregulates IL-1β/IL1R1 target genes (PTGES, COX2, RAGE, ABCG2) and promotes breast cancer cell migration and invasion. Gene expression studies; gene silencing; co-immunoprecipitation; ChIP assays; ELISA; cell migration and invasion assays; immunofluorescence Scientific reports Medium 27072893
2016 HNF4α is upregulated by H. pylori via NF-κB signaling and stimulates IL-1R1 expression; IL-1β/IL-1R1 then activates NF-κB, further increasing HNF4α in a feedback loop sustaining NF-κB activation and driving inflammation toward gastric cancer. Gene expression and protein studies in H. pylori-infected cells and clinical samples; NF-κB reporter assays; siRNA knockdown; co-immunoprecipitation Oncotarget Medium 26870992
2018 IL-1R1 activation in the injured kidney exacerbates cisplatin-induced acute kidney injury by inducing TNF production and polarizing intrarenal myeloid cells (macrophages, CD11bint/CD11cint cells, neutrophils) toward a proinflammatory TNF-producing phenotype; IL-1R1 KO mice had attenuated AKI with fewer Ly6G+ neutrophils. IL-1R1-/- mice; cisplatin nephrotoxicity model; serum creatinine/BUN; histology; machine learning analysis of intrarenal immune cells by flow cytometry; TNF measurement American journal of physiology. Renal physiology Medium 29790392
2018 IL-1R1 and MyD88 signaling in CD4+ T cells promotes Th17 differentiation and atherosclerotic plaque growth; transfer of IL-1R1-deficient CD4+ T cells reduced lesion development and Th17/IL-17 production compared with WT T cell recipients, and reduced plaque collagen content. Adoptive transfer of il1r1-/- or myd88-/- CD4+ T cells into rag1-/-apoe-/- mice; atherosclerosis quantification; Th17/IFN-γ cytokine production assays; human CD4+ T cell MyD88 inhibitor experiments Cardiovascular research Medium 29036304
2018 IL-1R1 signaling in intestinal epithelial cells (IECs) and IL-1R on corneal cells contribute to maintenance of a bacteria-free corneal surface; IL-1R-/- and MyD88-/- corneas harbored numerous metabolically active bacteria detectable by alkyne-D-alanine labeling, while wild-type corneas remained essentially sterile. IL-1R-/- and MyD88-/- mice; alkyne-functionalized D-alanine (alkDala) bacterial metabolic labeling; FISH for viable bacteria; fluorescein permeability assay; topical antibiotics control Frontiers in microbiology Medium 29896179
2023 IL-1R1 global knockout attenuated behavioral impairments and reactive microglia/astrocyte staining 14 weeks after closed-head injury; IL-1R1 signaling showed temporal specificity at 9 h post-injury, selectively upregulating chemokines Ccl2, Ccl3, Ccl4 in astrocytes while having limited impact on TNFα regulation. Global IL-1R1 knockout mice; closed-head injury TBI model; NanoString Neuroinflammatory panel (757 genes) at 3, 9, 24, 72 h; behavioral testing at 14 weeks; immunostaining for microglia and astrocytes Journal of neuroinflammation Medium 37884959
2018 IL-1α released by alveolar macrophages dying upon beryllium exposure upregulates CD80 on immature dendritic cells via IL-1R1, promoting their migration to lung-draining lymph nodes during beryllium sensitization; blocking IL-1R1 (and TLR9 together) prevented CD80hi DC accumulation in LDLNs. IL-1R1 agonist/antagonist treatment; bone marrow-derived DC stimulation assays; in vivo beryllium sensitization; flow cytometric analysis of CD80hi DCs in LDLNs; alveolar macrophage death assays Journal of immunology Medium 30185516
2024 IL-1α from diabetic wound keratinocytes induces Nlrp3 gene expression in wound macrophages through IL-1 receptor signaling; mechanistically, IL-1R signaling increases the histone demethylase JMJD3 in macrophages, which activates Nlrp3 transcription via H3K27me3 demethylation. JMJD3 myeloid-conditional KO mice (Jmjd3f/flyz2Cre+) showed reduced macrophage NLRP3 expression. In vitro keratinocyte-macrophage co-culture; IL-1α ELISA; IL-1R signaling blockade; ChIP for H3K27me3 at Nlrp3 locus; Jmjd3f/flyz2Cre+ conditional KO mice; diabetic wound healing model Diabetes High 38869447

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cellular and molecular life sciences : CMLS 373 18535784
1996 IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. The Journal of biological chemistry 197 8626725
2011 A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis research & therapy 195 21801403
2009 Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures. Blood 159 19299332
1992 Amino acids conserved in interleukin-1 receptors (IL-1Rs) and the Drosophila toll protein are essential for IL-1R signal transduction. The Journal of biological chemistry 155 1531143
1999 Identification and characterization of SIGIRR, a molecule representing a novel subtype of the IL-1R superfamily. Cytokine 151 10346978
2013 The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling. PloS one 119 23308247
2013 IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8⁺ T cell responses to influenza A virus. Nature immunology 119 23314004
2009 IL-1R type I-dependent hemopoietic stem cell proliferation is necessary for inflammatory granulopoiesis and reactive neutrophilia. Journal of immunology (Baltimore, Md. : 1950) 119 19414802
2018 T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells. Nature communications 113 30093707
2019 IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects. Nature medicine 106 30833749
2004 Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. Genes and immunity 104 15190266
2020 Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells. The Journal of clinical investigation 95 31935195
1990 Induction of an interleukin-1 receptor (IL-1R) on monocytic cells. Evidence that the receptor is not encoded by a T cell-type IL-1R mRNA. The Journal of biological chemistry 94 2148319
1998 Interleukin-1 receptor (IL-1R) liquid formulation development using differential scanning calorimetry. Pharmaceutical research 93 9523304
2023 IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer. Nature communications 91 37460545
2013 Associations between genetic polymorphisms in IL-33, IL1R1 and risk for inflammatory bowel disease. PloS one 88 23634226
1999 Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. Genomics 88 10191101
2007 Pellino proteins: novel players in TLR and IL-1R signalling. Journal of cellular and molecular medicine 87 17635639
2000 Identification and characterization of two members of a novel class of the interleukin-1 receptor (IL-1R) family. Delineation of a new class of IL-1R-related proteins based on signaling. The Journal of biological chemistry 84 10882729
2011 Efficacy and long-term follow-up of IL-1R inhibitor anakinra in adults with Still's disease: a case-series study. Arthritis research & therapy 80 21682863
2009 IL-1R signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 74 19535637
2016 GPER signalling in both cancer-associated fibroblasts and breast cancer cells mediates a feedforward IL1β/IL1R1 response. Scientific reports 72 27072893
2006 SIGIRR promotes resistance against Pseudomonas aeruginosa keratitis by down-regulating type-1 immunity and IL-1R1 and TLR4 signaling. Journal of immunology (Baltimore, Md. : 1950) 71 16785552
2020 The IL1β-IL1R signaling is involved in the stimulatory effects triggered by hypoxia in breast cancer cells and cancer-associated fibroblasts (CAFs). Journal of experimental & clinical cancer research : CR 70 32778144
2016 Inflammation-Related IL1β/IL1R Signaling Promotes the Development of Asbestos-Induced Malignant Mesothelioma. Cancer prevention research (Philadelphia, Pa.) 69 26935421
2013 IL-1R1 is required for dendritic cell-mediated T cell reactivation within the CNS during West Nile virus encephalitis. The Journal of experimental medicine 69 23460727
2019 MyD88 and IL-1R signaling drive antibacterial immunity and osteoclast-driven bone loss during Staphylococcus aureus osteomyelitis. PLoS pathogens 68 30978245
2015 IMQ-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome. European journal of immunology 65 26147228
2015 IL-1R signaling enables bystander cells to overcome bacterial blockade of host protein synthesis. Proceedings of the National Academy of Sciences of the United States of America 64 26034289
2013 IL-1R1 signaling facilitates Munro's microabscess formation in psoriasiform imiquimod-induced skin inflammation. The Journal of investigative dermatology 61 23407395
1997 Different pattern of interleukin-1 beta-(IL-1 beta), interleukin-1 receptor antagonist- (IL-1ra) and interleukin-1 receptor type I- (IL-1R tI) mRNA-expression in single preimplantation mouse embryos at various developmental stages. Journal of reproductive immunology 59 9292778
2015 SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. Journal of leukocyte biology 55 26590148
2018 BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation. The Journal of experimental medicine 51 30093533
2014 IL-1R1 signaling regulates CXCL12-mediated T cell localization and fate within the central nervous system during West Nile Virus encephalitis. Journal of immunology (Baltimore, Md. : 1950) 50 25200953
2017 The Interleukin (IL)-1R1 pathway is a critical negative regulator of PyMT-mediated mammary tumorigenesis and pulmonary metastasis. Oncoimmunology 49 28405519
2006 ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion. Journal of leukocyte biology 49 17099102
1996 GM-CSF, IL-8, IL-1R, TNF-alpha R, and HLA-DR in nasal epithelial cells in allergic rhinitis. American journal of respiratory and critical care medicine 48 8630619
2014 FcγRIIa cross-talk with TLRs, IL-1R, and IFNγR selectively modulates cytokine production in human myeloid cells. Immunobiology 47 25108563
2022 The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders. International journal of molecular sciences 46 35163653
2018 IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription. The Journal of biological chemistry 46 30093408
2010 Endothelial IL-1R1 is a critical mediator of EAE pathogenesis. Brain, behavior, and immunity 46 20854891
2005 Effects of complete Freund's adjuvant on immunohistochemical distribution of IL-1beta and IL-1R I in neurons and glia cells of dorsal root ganglion. Acta pharmacologica Sinica 46 15663898
1992 Molecular characterization of the interleukin-1 receptor (IL-1R) on monocytes and polymorphonuclear cells. Cytokine 46 1385988
2011 Role of Toll interleukin-1 receptor (IL-1R) 8, a negative regulator of IL-1R/Toll-like receptor signaling, in resistance to acute Pseudomonas aeruginosa lung infection. Infection and immunity 44 22025515
2021 Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts. Scientific reports 43 33436947
2010 Allelic variants of IL1R1 gene associate with severe hand osteoarthritis. BMC medical genetics 42 20353565
2013 Characterization of interleukin-1β in Helicobacter pylori-induced gastric inflammation and DNA methylation in interleukin-1 receptor type 1 knockout (IL-1R1(-/-)) mice. European journal of cancer (Oxford, England : 1990) 39 23664095
2011 Contributions of the MyD88-dependent receptors IL-18R, IL-1R, and TLR9 to host defenses following pulmonary challenge with Cryptococcus neoformans. PloS one 38 22039448
2020 Mining the PDB for Tractable Cases Where X-ray Crystallography Combined with Fragment Screens Can Be Used to Systematically Design Protein-Protein Inhibitors: Two Test Cases Illustrated by IL1β-IL1R and p38α-TAB1 Complexes. Journal of medicinal chemistry 37 32543856
2024 IL-1R signaling drives enteric glia-macrophage interactions in colorectal cancer. Nature communications 35 39030280
2011 A role of IL-1R1 signaling in the differentiation of Th17 cells and the development of autoimmune diseases. Self/nonself 35 21776333
2000 Characterization of new polymorphisms in the 5' UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1RI plasma level. Genes and immunity 35 11197691
2021 MyD88 oligomer size functions as a physical threshold to trigger IL1R Myddosome signaling. The Journal of cell biology 34 33956941
2018 Interleukin 1 receptor (IL-1R1) activation exacerbates toxin-induced acute kidney injury. American journal of physiology. Renal physiology 34 29790392
2018 Cutting Edge: IL-1R1 Mediates Host Resistance to Mycobacterium tuberculosis by Trans-Protection of Infected Cells. Journal of immunology (Baltimore, Md. : 1950) 33 30068597
2017 Influence of the total saponin fraction from Dioscorea nipponica Makino on TLR2/4-IL1R receptor singnal pathway in rats of gouty arthritis. Journal of ethnopharmacology 33 28456576
2018 A novel murine model for contact lens wear reveals clandestine IL-1R dependent corneal parainflammation and susceptibility to microbial keratitis upon inoculation with Pseudomonas aeruginosa. The ocular surface 32 30439473
2019 An oral alpha-galactosylceramide adjuvanted Helicobacter pylori vaccine induces protective IL-1R- and IL-17R-dependent Th1 responses. NPJ vaccines 31 31666991
2010 Dynamic cross-talk analysis among TNF-R, TLR-4 and IL-1R signalings in TNFalpha-induced inflammatory responses. BMC medical genomics 31 20497537
2008 IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis. Iranian journal of allergy, asthma, and immunology 31 18322311
2022 Active-site molecular docking of nigellidine with nucleocapsid-NSP2-MPro of COVID-19 and to human IL1R-IL6R and strong antioxidant role of Nigella sativa in experimental rats. Journal of drug targeting 30 32875925
2021 A MyD88/IL1R Axis Regulates PD-1 Expression on Tumor-Associated Macrophages and Sustains Their Immunosuppressive Function in Melanoma. Cancer research 30 33619117
2018 Regulation of epithelial injury and bile duct obstruction by NLRP3, IL-1R1 in experimental biliary atresia. Journal of hepatology 30 29886157
2012 The toll interleukin-1 receptor (IL-1R) 8/single Ig domain IL-1R-related molecule modulates the renal response to bacterial infection. Infection and immunity 30 22890991
2018 IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis. Cardiovascular research 28 29036304
2015 Identification of potential small molecule allosteric modulator sites on IL-1R1 ectodomain using accelerated conformational sampling method. PloS one 28 25706624
2015 Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod expressions induced by TLR and IL-1R signaling in bone marrow stromal cells. Inflammation 27 25125146
2018 IL-1R and MyD88 Contribute to the Absence of a Bacterial Microbiome on the Healthy Murine Cornea. Frontiers in microbiology 26 29896179
1996 The combination of endotoxin and dexamethasone induces type II interleukin 1 receptor (IL-1r II) in monocytes: a comparison to interleukin 1 beta (IL-1 beta) and interleukin 1 receptor antagonist (IL-1ra). Cytokine 26 9047079
2016 T-cell-intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy. Proceedings of the National Academy of Sciences of the United States of America 25 26787865
2013 Blockade of IL-1R signaling diminishes Paneth cell depletion and Toxoplasma gondii induced ileitis in mice. American journal of clinical and experimental immunology 25 23885328
2019 Amyloid-beta impairs TOM1-mediated IL-1R1 signaling. Proceedings of the National Academy of Sciences of the United States of America 24 31570577
1993 Immunomodulatory activity of recombinant IL-1 receptor (IL-1-R) on models of experimental rheumatoid arthritis. Agents and actions 24 8273547
2015 Association of TNF-α-(308(GG)), IL-10(-819(TT)), IL-10(-1082(GG)) and IL-1R1(+1970(CC)) genotypes with the susceptibility and progression of leprosy in North Indian population. Cytokine 23 25697140
2006 Gene regulation by IL-1beta independent of IL-1R1 in the mouse brain. Glia 23 16358337
2015 IL-1A rs1800587, IL-1B rs1143634 and IL-1R1 rs2234650 polymorphisms in Iranian patients with systemic sclerosis. International journal of immunogenetics 21 26416393
2004 The 3' untranslated region of the membrane-bound IL-1R accessory protein mRNA confers tissue-specific destabilization. Journal of immunology (Baltimore, Md. : 1950) 21 15528363
2023 IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury. Journal of neuroinflammation 20 37884959
2018 Development of a Novel Backbone Cyclic Peptide Inhibitor of the Innate Immune TLR/IL1R Signaling Protein MyD88. Scientific reports 20 29930295
2023 IEC-intrinsic IL-1R signaling holds dual roles in regulating intestinal homeostasis and inflammation. The Journal of experimental medicine 19 36976181
2021 Impact of IL-1β and the IL-1R antagonist on relapse risk and survival in AML patients undergoing immunotherapy for remission maintenance. Oncoimmunology 19 34367728
2015 (15)O-Water PET Study of the Effect of Imatinib, a Selective Platelet-Derived Growth Factor Receptor Inhibitor, Versus Anakinra, an IL-1R Antagonist, on Water-Perfusable Tissue Fraction in Colorectal Cancer Metastases. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 19 26069310
2010 A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis. Arthritis research & therapy 19 20950476
2017 Association of genetic polymorphisms in IL-1R1 and IL-1R2 genes with IgA nephropathy in the Han Chinese population. Oncotarget 18 28881593
2015 IL-1R1 is expressed on both Helios(+) and Helios(-) FoxP3(+) CD4(+) T cells in the rheumatic joint. Clinical and experimental immunology 18 26076982
2023 M1-Type Microglia-Derived Extracellular Vesicles Overexpressing IL-1R1 Promote Postoperative Cognitive Dysfunction by Regulating Neuronal Inflammation. Inflammation 17 37505422
2022 Inhibition of IL1R1 or CASP4 attenuates spinal cord injury through ameliorating NLRP3 inflammasome-induced pyroptosis. Frontiers in immunology 17 35990672
2019 microRNA-21 negatively regulates NF-κB signaling pathway via targeting IL1R1 in miiuy croaker. Developmental and comparative immunology 17 31869675
2018 IL-1R and Inflammasomes Mediate Early Pulmonary Protective Mechanisms in Respiratory Brucella Abortus Infection. Frontiers in cellular and infection microbiology 17 30456207
2015 Serum CD121a (Interleukin 1 Receptor, Type I): A Potential Novel Inflammatory Marker for Coronary Heart Disease. PloS one 17 26098632
2017 IL1R1 gene polymorphisms are associated with knee osteoarthritis risk in the Chinese Han population. Oncotarget 16 27980229
1991 Binding of IL-1 beta to IL-1R type II at single cell level. Journal of immunology (Baltimore, Md. : 1950) 16 1831828
2024 Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris. PLoS pathogens 15 39536069
2024 Localization of brain neuronal IL-1R1 reveals specific neural circuitries responsive to immune signaling. Journal of neuroinflammation 15 39563437
2022 Intratumoral IL-1R1 expression delineates a distinctive molecular subset with therapeutic resistance in patients with gastric cancer. Journal for immunotherapy of cancer 15 35110359
2018 TLR9 and IL-1R1 Promote Mobilization of Pulmonary Dendritic Cells during Beryllium Sensitization. Journal of immunology (Baltimore, Md. : 1950) 15 30185516
2016 Mutual amplification of HNF4α and IL-1R1 composes an inflammatory circuit in Helicobacter pylori associated gastric carcinogenesis. Oncotarget 15 26870992
2009 TRAF6 promotes ubiquitination and regulated intramembrane proteolysis of IL-1R1. Biochemical and biophysical research communications 15 19232518
2024 Diabetic Wound Keratinocytes Induce Macrophage JMJD3-Mediated Nlrp3 Expression via IL-1R Signaling. Diabetes 14 38869447

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