Affinage

IL4R

Interleukin-4 receptor subunit alpha · UniProt P24394

Length
825 aa
Mass
89.7 kDa
Annotated
2026-06-10
96 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL4R encodes IL-4Rα, the shared α-chain that pairs with IL-13Rα1 to reconstitute a high-affinity IL-13 receptor and to transduce both IL-4 and IL-13 signals through STAT6 (PMID:9013879). Ligand engagement triggers rapid tyrosine phosphorylation of IL-4Rα and STAT6 activation, which drives target outputs such as endothelial MCP-1 induction (PMID:9301536). The cytoplasmic tail partitions distinct outputs across discrete tyrosine modules: Y497 and Y713 deliver an anti-apoptotic survival signal that is separable from and antagonized by the STAT6-docking domain (PMID:9670964), while the membrane-proximal ID-1 region and its first conserved tyrosine (Y1) initiate STAT6-independent PI3K/mTOR signaling required for G2/M cell-cycle completion (PMID:16210622), and an acidic motif supports proto-oncogene (c-junB/c-fos) induction (PMID:9619370). Through these branches IL-4Rα governs Th2-type immunity and tissue effector programs, including alternative macrophage activation in the hematopoietic compartment (PMID:18354220) and smooth-muscle hypercontractility that drives helminth egg expulsion (PMID:20360135); in the nervous system, IL-4Rα on inhibitory GABAergic neurons is required for contextual fear memory via BDNF/TrkB and ARC pathways (PMID:34793707). Disease-linked coding variants rewire signaling: the asthma-associated R576 allele recruits the GRB2 adaptor to redirect output toward ERK→IL-6→STAT3 and TH17 reprogramming (PMID:27479084), and the somatic transmembrane mutation I242N in primary mediastinal large B-cell lymphoma causes constitutive JAK-STAT activation and confers a growth advantage (PMID:29467182). Surface IL-4Rα abundance is set post-transcriptionally—suppressed by glucocorticoids (PMID:9847438), maintained on mast cells by an IL-3→Tyk2→STAT6→HSP90 axis (PMID:36440951), tuned by intronic SNPs controlling the soluble exon-8 isoform (PMID:16917945), and repressed by IGF2BP3-mediated mRNA destabilization [PMID:bio_10.1101_2025.07.19.665669].

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Established that IL-4Rα is the obligate shared subunit linking IL-4 and IL-13 to a common signaling output, resolving how two cytokines converge on STAT6.

    Evidence Reconstitution of IL-4Rα with IL-13Rα1 in CHO cells with radioligand binding and STAT6 EMSA; neutralizing anti-IL-4Rα block of IL-13-induced MCP-1 in endothelial cells

    PMID:9013879 PMID:9301536

    Open questions at the time
    • Stoichiometry and kinetics of receptor heterodimer assembly not resolved
    • Identity of the JAK partners engaged was not directly mapped in these studies
  2. 1998 High

    Showed that the IL-4Rα cytoplasmic tail is modular, with distinct tyrosine and sequence motifs separating survival, proliferation, and proto-oncogene outputs from STAT6 signaling.

    Evidence Domain-swap chimeras and Y→F mutagenesis in 32D/BA/F3 cells; apoptosis and proto-oncogene induction assays

    PMID:9619370 PMID:9670964

    Open questions at the time
    • Direct effector recruited at Y497/Y713 not identified
    • Whether STAT6-domain antagonism of survival is competitive or active was not defined
  3. 1998 Medium

    Defined post-transcriptional control of IL-4Rα surface levels, distinguishing translational suppression from mRNA-stability regulation by glucocorticoids.

    Evidence Flow cytometry, Northern blot, nuclear run-on and mRNA half-life analysis with dexamethasone/RU486

    PMID:9847438

    Open questions at the time
    • The cis-elements and trans-factors mediating mRNA destabilization were not identified
    • Stimulus-specific (IL-4 vs PMA) divergence in mechanism not fully explained
  4. 1998 High

    Located a STAT6-independent proliferative arm, mapping the ID-1 region and Y1 to PI3K/mTOR-dependent cell-cycle progression.

    Evidence Tyrosine mutagenesis and chimeric receptors with rapamycin treatment and p70S6K/BrdU readouts in primary T cells

    PMID:16210622

    Open questions at the time
    • Direct adaptors coupling ID-1/Y1 to PI3K were not identified
    • How S-phase entry proceeds in tyrosine-deficient receptor remains unexplained
  5. 1999 Medium

    Tested whether the allergy-associated Q576R/Y575F coding changes alter canonical signaling, finding no measurable effect on phosphorylation, STAT6, proliferation, or survival.

    Evidence Mutagenesis of human IL-4Rα in murine cells with phosphorylation, EMSA, proliferation, apoptosis, and CD23 readouts

    PMID:10201973

    Open questions at the time
    • Negative result in a heterologous murine system may miss context-dependent effects
    • Non-canonical outputs (later shown for R576) were not assessed
  6. 2001 Medium

    Revealed that IL-13 effector functions in the lung can proceed via a STAT6-dependent but IL-4Rα-independent route, indicating non-redundant receptor usage.

    Evidence Adoptive T-cell transfer into IL-4Rα- and STAT6-deficient mice with airway hyperreactivity and BALF readouts

    PMID:11466392

    Open questions at the time
    • The alternative receptor component used by IL-13 was not molecularly defined
    • Cell type transducing the IL-4Rα-independent signal not identified
  7. 2004 Medium

    Dissected receptor antagonism and allelic gain-of-function, showing IL-13 contact residues at IL-4Rα and that STAT6 potency can be uncoupled from Th2 differentiation.

    Evidence IL-13 E13K competition/blocking across type I/II/III receptor cells; I50 vs V50 variant transduction in primary T cells with reporter and differentiation assays

    PMID:15331327 PMID:15383584

    Open questions at the time
    • Structural basis of E13–IL-4Rα contact not solved
    • Mechanism decoupling STAT6 activity from Th2 commitment unknown
  8. 2006 Medium

    Identified intronic splicing SNPs and the splicing factors that set the ratio of membrane versus soluble IL-4Rα.

    Evidence IL4R minigene splicing assays with variant constructs, human mRNA RT-PCR, and SRp20/YT521-B overexpression

    PMID:16917945

    Open questions at the time
    • Functional consequence of altered soluble isoform on signaling not quantified
    • Direct binding of SRp20/YT521-B to the variant sites not shown
  9. 2010 High

    Established cell-compartment-specific roles in vivo, separating hematopoietic IL-4Rα (macrophage activation, protection) from smooth-muscle IL-4Rα (hypercontractility and egg expulsion).

    Evidence Reciprocal bone marrow chimeras and SM-MHC-Cre smooth-muscle conditional knockout in S. mansoni infection

    PMID:18354220 PMID:20360135

    Open questions at the time
    • Downstream signaling within smooth muscle not mapped
    • Molecular basis of compartment-specific protective vs fibrotic outcomes unresolved
  10. 2011 Medium

    Extended IL-4Rα signaling to tumor survival and metastasis through parallel JAK1/STAT6 and JNK/ERK and Akt/MAPK arms.

    Evidence siRNA knockdown in HCC and in vitro/in vivo neutralizing antibody studies in rhabdomyosarcoma models with metastasis endpoints

    PMID:21536546 PMID:28665449

    Open questions at the time
    • Relative contribution of each downstream arm to metastasis not isolated
    • Receptor type (I vs II) driving tumor signaling not defined
  11. 2016 High

    Demonstrated that a single coding variant reprograms signaling output, with R576 recruiting GRB2 to drive an ERK→IL-6→STAT3 TH17 axis underlying allergic pathology.

    Evidence Il4ra^R576 knock-in mice, Treg-specific Il6ra/Rorc conditional KO, IL-4Rα–GRB2 Co-IP, phospho-ERK/STAT3 assays, and in vivo IL-6 neutralization

    PMID:27479084

    Open questions at the time
    • Structural mechanism by which R576 creates a GRB2 docking site not solved
    • Human relevance of the Treg-to-TH17 conversion not directly tested
  12. 2018 High

    Identified somatic IL4R gain-of-function mutation as an oncogenic driver causing constitutive JAK-STAT activation in lymphoma.

    Evidence Sequencing of PMBCL cases, functional STAT-phosphorylation and cytokine assays of I242N, and mouse xenotransplantation

    PMID:29467182

    Open questions at the time
    • Mechanism by which the transmembrane I242N enforces ligand-independent dimerization not defined
    • Therapeutic vulnerability of the mutant not established
  13. 2021 High

    Uncovered a neuronal, cell-type-specific function for IL-4Rα in memory, acting in inhibitory neurons via BDNF/TrkB and ARC plasticity pathways.

    Evidence Neuron-subtype conditional and global IL-4Rα knockouts with fear conditioning, Morris water maze, snRNA-seq, and pathway immunoblots

    PMID:33020569 PMID:34793707

    Open questions at the time
    • Ligand source and proximal signaling in GABAergic neurons not defined
    • Link between receptor activation and ARC/BDNF induction mechanistically incomplete
  14. 2021 High

    Showed IL-4Rα signaling is selectively required for some but not all macrophage activation markers, and identified an IL-4Rα-dependent ERK-driven role in osteoclast precursor proliferation.

    Evidence CX3CR1-Cre macrophage conditional KO and mixed bone marrow chimeras; bone metastasis model with IL-4 deficiency and ERK inhibition

    PMID:34329367 PMID:34863091

    Open questions at the time
    • Pathway driving IL-4Rα-independent RELMα induction unknown
    • Whether type I receptor exclusively mediates OCP proliferation not confirmed
  15. 2022 Medium

    Defined how surface receptor density is actively maintained, identifying an IL-3→Tyk2→STAT6→HSP90 axis sustaining IL-4Rα on mast cells.

    Evidence Pharmacological inhibition of Tyk2/STAT6/HSP90 with flow cytometry for surface IL-4Rα and cytokine ELISA

    PMID:36440951

    Open questions at the time
    • How HSP90 stabilizes IL-4Rα protein not mechanistically resolved
    • Generality beyond mast cells not tested
  16. 2025 Medium

    Identified an m6A-reader-dependent post-transcriptional brake on receptor expression, with IGF2BP3 destabilizing IL4R and IL13RA1 mRNAs to limit STAT6 signaling.

    Evidence RIP, mRNA stability assays, surface receptor flow cytometry, and phospho-STAT6 readouts in primary airway epithelial cells (preprint)

    PMID:bio_10.1101_2025.07.19.665669

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • m6A sites on IL4R mediating IGF2BP3 binding not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct cytoplasmic motifs are selected to bias survival, proliferation, STAT6, or GRB2-rerouted outputs in a given cell type, and how the layered post-transcriptional controls integrate to set receptor density in vivo, remain unresolved.
  • No structural model linking variant-driven adaptor recruitment to output switching
  • Quantitative integration of glucocorticoid, IL-3, splicing-SNP, and IGF2BP3 controls on surface IL-4Rα not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-1643685 Disease 2
Partners
GRB2IGF2BP3IL13RA1STAT6
Complex memberships
Type I IL-4 receptor (IL-4Rα/γc)Type II IL-4 receptor (IL-4Rα/IL-13Rα1)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Co-expression of IL-4Rα with IL-13Rα1 reconstitutes a high-affinity IL-13 receptor complex (Kd ~30 pM) that allows cross-competition of IL-13 and IL-4 and enables STAT6 activation by both cytokines; neither subunit alone supports STAT6 activation or high-affinity IL-13 binding. Reconstitution in CHO cells, radioligand binding, electrophoretic mobility shift assay (EMSA) for STAT6 FEBS letters High 9013879
1997 IL-13 signals through IL-4Rα on human endothelial cells to induce MCP-1 expression: a neutralizing anti-IL-4Rα monoclonal antibody blocks IL-13-induced MCP-1; IL-4Rα undergoes rapid tyrosine phosphorylation after IL-13 or IL-4 stimulation; both cytokines activate STAT6 in these cells. Neutralizing antibody blockade, immunoprecipitation with anti-phosphotyrosine detection, ELISA, in situ hybridization Immunology Medium 9301536
1998 IL-4Rα cytoplasmic domains containing Y497 and Y713 positively signal protection from apoptosis; transplantation of these tyrosine-containing domains to a truncated IL-2Rβ confers IL-4-dependent anti-apoptotic signaling, while the STAT6-docking tyrosine domain suppresses this protection. Y497F and Y713F mutations abolish protection. Cytoplasmic domain transplantation chimeras, site-directed mutagenesis (Y→F), apoptosis assay in 32D cells Journal of immunology High 9670964
1998 IL-4-induced upregulation of IL-4Rα surface expression is suppressed by dexamethasone at the translational or post-translational level (mRNA levels unchanged), whereas PMA-induced IL-4Rα expression is suppressed by dexamethasone through decreased mRNA stability (post-transcriptional mechanism). The effect is glucocorticoid-receptor-dependent and reversed by RU486. Flow cytometry, Northern blot, nuclear run-on transcription assay, mRNA half-life analysis The Journal of allergy and clinical immunology Medium 9847438
1998 IL-4Rα requires an intact ID-1 (membrane-proximal) region for STAT6-independent proliferative signaling; the Y1 residue (first conserved cytoplasmic tyrosine) initiates PI3K/mTOR pathway activation required for G2/M cell-cycle completion. Tyrosine-deficient IL-4Rα can still signal S-phase entry and STAT5 phosphorylation if the ID-1 region is intact. Site-directed mutagenesis of cytoplasmic tyrosines, chimeric receptor constructs, cell-cycle analysis (BrdU/PI), p70S6K phosphorylation assay, rapamycin treatment in primary T cells Journal of immunology High 16210622
1998 Acidic motif of IL-4Rα can substitute for the A-region of IL-2Rβ to support c-junB and c-fos induction when transplanted into chimeric receptors, indicating a functional role for the IL-4Rα acidic domain in proto-oncogene induction; however, exchange of the S-region with IL-4Rα sequence abolishes all IL-2R functions. Cytoplasmic domain chimeras stably transfected into BA/F3 cells, proto-oncogene mRNA induction assay Cytokine Medium 9619370
1999 The allergy-associated human IL-4Rα Q576R (equivalent to Q551R in some numbering) and adjacent Y575F mutations do not significantly alter tyrosine phosphorylation, STAT6 DNA-binding, proliferation, protection from apoptosis, or CD23 induction in response to IL-4 compared with wild-type receptor in murine cells. Mutagenesis of human IL-4Rα cDNA expressed in murine cells, phosphorylation assays, EMSA, proliferation assay, apoptosis assay, CD23 induction by flow cytometry Journal of immunology Medium 10201973
2001 T cell-derived IL-13 can induce airway hyperreactivity, mucus hypersecretion, and eosinophilia independently of IL-4Rα (in IL-4Rα-deficient hosts), but this IL-13 signaling requires STAT6, indicating IL-13 can utilize a STAT6-dependent but IL-4Rα-independent receptor component in the lung. Adoptive transfer of IL-13+/+ or IL-13-/- CD4+ T cells into wild-type, IL-4Rα-deficient, or STAT6-deficient mice; airway hyperreactivity measurement; BALF eosinophil counts Journal of immunology Medium 11466392
2004 IL-4Rα allelic variant I50 (isoleucine at position 50) acts as a gain-of-function variant relative to V50 for STAT6-dependent transcriptional activity but does not increase Th2 differentiation efficiency, IL-4-mediated Th1 repression, or IL-4-induced proliferation, indicating that gain-of-function with respect to STAT6 is dissociated from effects on Th2/Th1 induction. Retroviral transduction of primary T cells with I50 vs. V50 IL-4Rα variants; STAT6 reporter assays; Th2 differentiation assay; proliferation assay Journal of immunology Medium 15383584
2004 IL-13 mutant E13K (IL-13E13K) blocks IL-4 signaling through type II IL-4R (IL-4Rα/IL-13Rα1 complex) by competing with IL-4 for binding to IL-4Rα and preventing IL-13Rα1–IL-4Rα heterodimerization, but does not inhibit IL-4 binding or signaling through the type I receptor (IL-4Rα/γc). The glutamate at position 13 of IL-13 contacts IL-4Rα. Competitive binding assay, STAT6 phosphorylation assay, protein synthesis inhibition assay in cells expressing type I, II, or III IL-4R Cellular immunology Medium 15331327
2006 Common intronic SNPs flanking the alternatively-spliced exon 8 of IL4R (c.912-1003A>G, c.912-833T>C, c.912-630A>G, c.912-577A>G) regulate alternative splicing of IL4R: the minor allele haplotype significantly decreases production of the soluble IL-4Rα isoform (exon 8+ variant), an effect dependent on splicing factors SRp20 and YT521-B. IL4R minigene splicing assay with variant constructs, RT-PCR on human mRNA from patients and controls, splicing factor overexpression Human mutation Medium 16917945
2008 IL-4Rα expression specifically on bone marrow-derived cells (hematopoietic compartment) is necessary and sufficient to protect mice against severe inflammation in acute schistosomiasis and to generate alternatively activated macrophages; IL-4Rα expression on non-bone marrow-derived cells regulates granuloma size and fibrosis but cannot prevent severe hepatic/intestinal pathology or endotoxemia. Bone marrow chimera experiments (reciprocal transplants between wild-type and IL-4Rα-deficient mice), cytokine measurement, macrophage phenotyping, survival analysis Journal of immunology High 18354220
2010 IL-4Rα signaling in smooth muscle cells mediates IL-4/IL-13-dependent intestinal hypercontractility required for egg expulsion during acute schistosomiasis; smooth muscle cell-specific IL-4Rα deletion (SM-MHC-Cre) increased weight loss and early mortality without intestinal tissue damage, despite intact Th2 responses. Smooth muscle cell-specific conditional IL-4Rα knockout (SM-MHCCre × IL-4Rαfl/flox), S. mansoni infection, intestinal contractility measurement, egg expulsion quantification American journal of physiology. Gastrointestinal and liver physiology High 20360135
2011 IL-4R knockdown in HCC cells abolishes IL-4-induced activation of JAK1/STAT6 and JNK/ERK1/2 signaling pathways and results in enhanced apoptosis, impaired proliferation, and reduced invasion, demonstrating that IL-4R drives HCC cell survival and metastasis through these two parallel downstream pathways. siRNA knockdown of IL-4R in HCC cell lines, Western blot for pathway activation, flow cytometry for apoptosis/cell cycle, invasion assay The International journal of biological markers Medium 28665449
2011 IL-4 and IL-13 acting through IL-4Rα activate STAT6, Akt, and MAPK signaling in rhabdomyosarcoma cells, promote tumor cell proliferation, and suppress myogenic differentiation factors MyoD and Myogenin; neutralizing IL-4Rα antibody in vivo reduces lymph node and pulmonary metastases and extends survival in a genetically engineered mouse model. In vitro signaling assays (Western blot), differentiation factor immunoblotting, in vivo neutralizing antibody treatment in ARMS mouse model, metastasis quantification Clinical cancer research Medium 21536546
2016 The asthma-associated IL-4Rα R576 variant (Il4ra^R576) promotes conversion of induced Treg cells to TH17 fate by recruiting the GRB2 adaptor protein, which activates ERK→IL-6→STAT3 signaling to drive IL-17 expression; Treg-specific deletion of Il6ra or Rorc (but not Il4 or Il13) prevented exacerbated airway inflammation in Il4ra^R576 mice. Knock-in mouse model (Il4ra^R576), Treg-specific conditional KO of Il6ra and Rorc, Co-IP (IL-4Rα–GRB2 interaction), phospho-ERK/STAT3 assays, IL-6 neutralization in vivo Nature medicine High 27479084
2018 Somatic IL4R mutations in primary mediastinal large B-cell lymphoma (particularly I242N in the transmembrane domain) are gain-of-function mutations that cause constitutive JAK-STAT pathway activation, upregulate downstream cytokine expression, and confer growth advantage in a mouse xenotransplantation model. Sequencing of primary PMBCL cases and cell lines, functional assays of I242N mutant IL4R (STAT phosphorylation, cytokine profiling), mouse xenotransplantation model Blood High 29467182
2021 IL-4Rα expressed on inhibitory (GABAergic) neurons, but not excitatory neurons, is required for contextual fear memory; IL-4Rα knockout specifically in inhibitory neurons disrupts BDNF/TrkB and ARC signaling pathways associated with synaptic plasticity, impairing episodic memory. Neuron-subtype-specific IL-4Rα conditional KO (Cre-lox), contextual fear conditioning behavioral assay, snRNA-seq, BDNF/TrkB/ARC pathway analysis Neuron High 34793707
2020 IL-4Rα deficiency impairs reference memory (but not spatial learning) and disrupts activation of hippocampal BDNF/TrkB and ARC signaling pathways during the memory phase. Morris water maze in IL-4Rα-deficient vs. IL-4/IL-13 double-deficient vs. wild-type mice; Western blot for BDNF/TrkB and ARC pathway components Scientific reports Medium 33020569
2021 IL-4/IL-4Rα type I receptor signaling in osteoclast precursors (OCPs) promotes OCP proliferation via ERK pathway activation; neutrophils are the main source of IL-4 in bone marrow; IL-4-deficient mice show reduced OCP proliferation; ERK antagonism with ravoxertinib prevents bone destruction. Mouse bone metastasis model, BrdU proliferation assay, transcriptomic profiling of OCPs, IL-4 deficiency experiment, ERK inhibitor treatment, Western blot Molecular medicine Medium 34863091
2022 IL-3 maintains constitutive IL-4Rα (CD124) surface expression on mast cells via a Tyk2→STAT6→HSP90 signaling axis; inhibition of Tyk2, STAT6, or HSP90 impairs IL-3-induced IL-4Rα upregulation, and this IL-3-maintained IL-4Rα expression is required for IL-4 costimulation of IL-33-induced IL-6 and IL-13 production. Pharmacological inhibition of Tyk2, STAT6, and HSP90 in mast cell cultures; flow cytometry for IL-4Rα surface expression; cytokine ELISA Immunology Medium 36440951
2021 RELMα+ alternatively activated colonic macrophages induced during Trichuris muris infection acquire their phenotype through a cell-intrinsic IL-4Rα-independent mechanism; in contrast, PD-L2 expression on these macrophages is dependent on IL-4Rα signaling. Macrophage-specific IL-4Rα conditional KO (IL-4Rαfl/fl × CX3CR1Cre), IL-4Rα-deficient/wild-type mixed bone marrow chimeras, flow cytometry for macrophage surface markers PLoS pathogens High 34329367
2025 IGF2BP3, an RNA-binding protein, directly binds IL4R and IL13RA1 mRNAs, stabilizing them via an m6A-dependent mechanism; IGF2BP3 depletion increases IL4R and IL13RA1 mRNA half-life, elevates IL-4Rα and IL-13Rα1 surface expression, and enhances IL-13/IL-4-dependent STAT6 phosphorylation, identifying IGF2BP3 as a post-transcriptional repressor of IL-4Rα expression. RNA immunoprecipitation (RIP), mRNA stability assay, flow cytometry for receptor surface expression, phospho-STAT6 assay, genome-wide transcriptional analysis in primary airway epithelial cells bioRxiv (preprint)preprint Medium bio_10.1101_2025.07.19.665669

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Cloning of the human IL-13R alpha1 chain and reconstitution with the IL4R alpha of a functional IL-4/IL-13 receptor complex. FEBS letters 185 9013879
2010 Control of RSV-induced lung injury by alternatively activated macrophages is IL-4R alpha-, TLR4-, and IFN-beta-dependent. Mucosal immunology 178 20404812
1998 Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Current biology : CB 171 9635196
2016 An asthma-associated IL4R variant exacerbates airway inflammation by promoting conversion of regulatory T cells to TH17-like cells. Nature medicine 155 27479084
2006 IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression. American journal of respiratory and critical care medicine 118 17170387
2001 IL-13 induces airways hyperreactivity independently of the IL-4R alpha chain in the allergic lung. Journal of immunology (Baltimore, Md. : 1950) 113 11466392
2021 GABAergic neuronal IL-4R mediates T cell effect on memory. Neuron 90 34793707
2015 Targeting IL4/IL4R for the treatment of epithelial cancer metastasis. Clinical & experimental metastasis 81 26385103
2009 Airway and lung pathology due to mucosal surface dehydration in {beta}-epithelial Na+ channel-overexpressing mice: role of TNF-{alpha} and IL-4R{alpha} signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment. Journal of immunology (Baltimore, Md. : 1950) 74 19299736
2022 IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases. Allergy 66 36445014
2003 Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. American journal of human genetics 64 12748907
1991 The interleukin-4 receptor gene (IL4R) maps to 16p11.2-16p12.1 in human and to the distal region of mouse chromosome 7. Genomics 64 1679753
2006 Association of the IL4R single-nucleotide polymorphism I50V with rapidly erosive rheumatoid arthritis. Arthritis and rheumatism 61 16646030
2012 Polymorphisms of TREH, IL4R and CCDC26 genes associated with risk of glioma. Cancer epidemiology 60 22369735
2002 Association of IL4R haplotypes with type 1 diabetes. Diabetes 54 12401728
1999 Cutting edge: effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction. Journal of immunology (Baltimore, Md. : 1950) 53 10201973
2008 Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents. Jornal de pediatria 52 18425216
1997 Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation. Immunology 52 9301536
2011 IL-4R drives dedifferentiation, mitogenesis, and metastasis in rhabdomyosarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research 49 21536546
2010 Immunomodulation with IL-4R alpha antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease. Journal of immunology (Baltimore, Md. : 1950) 47 20861354
2018 Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to constitutive JAK-STAT signaling activation. Blood 46 29467182
2004 Common variants within the interleukin 4 receptor alpha gene (IL4R) are associated with susceptibility to osteoarthritis. Human genetics 41 14745651
1998 Regulation of apoptosis by tyrosine-containing domains of IL-4R alpha: Y497 and Y713, but not the STAT6-docking tyrosines, signal protection from apoptosis. Journal of immunology (Baltimore, Md. : 1950) 40 9670964
2007 Association between Q551R IL4R genetic variants and atopic asthma risk demonstrated by meta-analysis. The Journal of allergy and clinical immunology 39 17586032
2006 IL-4R signaling is required to induce IL-10 for the establishment of T(h)2 dominance. International immunology 39 16940042
1998 Glucocorticoids inhibit IL-4 and mitogen-induced IL-4R alpha chain expression by different posttranscriptional mechanisms. The Journal of allergy and clinical immunology 39 9847438
2012 IL1B, IL4R, IL12RB1 and TNF gene polymorphisms are associated with Plasmodium vivax malaria in Brazil. Malaria journal 34 23217179
2003 Polymorphisms in the IL-4 and IL-4R [alpha] genes and allergic asthma. Clinical chemistry and laboratory medicine 34 12940513
2008 IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis. Journal of immunology (Baltimore, Md. : 1950) 31 18354220
2013 B cell activation through CD40 and IL4R ligation modulates the response of chronic lymphocytic leukaemia cells to BAFF and APRIL. British journal of haematology 30 24245956
2011 Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers' pneumoconiosis in China: a case-control study. PloS one 30 21857939
2014 Increased Th17 cell frequency and poor clinical outcome in rheumatoid arthritis are associated with a genetic variant in the IL4R gene, rs1805010. Arthritis & rheumatology (Hoboken, N.J.) 28 24782180
2012 Polymorphisms in the IL-13 and IL-4R genes are associated with the development of renal cell carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology 26 22317767
2019 Susceptibility to L. sigmodontis infection is highest in animals lacking IL-4R/IL-5 compared to single knockouts of IL-4R, IL-5 or eosinophils. Parasites & vectors 25 31109364
1995 Modulation of the immunoglobulin dysregulation in GvH- and SLE-like diseases by the murine IL-4 receptor (IL-4-R). Inflammation research : official journal of the European Histamine Research Society ... [et al.] 23 8548394
2020 IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory. Scientific reports 22 33020569
2013 Association of genetic variants in the IL4 and IL4R genes with the severity of joint damage in rheumatoid arthritis: a study in seven cohorts. Arthritis and rheumatism 22 23983153
2014 Novel HIV IL-4R antagonist vaccine strategy can induce both high avidity CD8 T and B cell immunity with greater protective efficacy. Vaccine 21 25151041
2011 Influence of chemotherapy on nitric oxide synthase, indole-amine-2,3-dioxygenase and CD124 expression in granulocytes and monocytes of non-small cell lung cancer. Cancer science 21 22107611
2017 IL-4R suppresses airway inflammation in bronchial asthma by inhibiting the IL-4/STAT6 pathway. Pulmonary pharmacology & therapeutics 20 28093225
2017 Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A Meta-Analysis. Disease markers 20 28392616
2005 Sequence motifs in IL-4R alpha mediating cell-cycle progression of primary lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 20 16210622
2016 Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells. Oncology reports 19 27220374
2010 IL-4R{alpha}-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis. American journal of physiology. Gastrointestinal and liver physiology 19 20360135
2007 Association of IL4R gene polymorphisms with asthma in Chinese populations. Human mutation 18 17823973
2004 Analysis of IL4R haplotypes in predisposition to multiple sclerosis. Genes and immunity 18 14712310
2020 Detection of association of IL1β, IL4R, and IL6 gene polymorphisms with cervical cancer in the Bangladeshi women by tetra-primer ARMS-PCR method. International immunopharmacology 17 33187912
2006 TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects. Human genetics 17 17115186
2004 Mechanism of action of interleukin-13 antagonist (IL-13E13K) in cells expressing various types of IL-4R. Cellular immunology 17 15331327
2011 Ten-color flow cytometry reveals distinct patterns of expression of CD124 and CD126 by developing thymocytes. BMC immunology 15 21689450
2003 Polymorphisms of IL-4, IL-4R alpha, and AICDA genes in adult allergic asthma. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 15 12973929
2004 An IL-4R alpha allelic variant, I50, acts as a gain-of-function variant relative to V50 for Stat6, but not Th2 differentiation. Journal of immunology (Baltimore, Md. : 1950) 14 15383584
2018 Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies. Scientific reports 13 29459738
2014 Impact of single nucleotide polymorphism in IL-4, IL-4R genes and systemic concentration of IL-4 on the incidence of glioma in Iraqi patients. International journal of medical sciences 13 25170298
2003 No evidence for involvement of IL-4R and CD11B from the IBD1 region and STAT6 in the IBD2 region in Crohn's disease. European journal of human genetics : EJHG 13 14571275
1996 Expression of IL-2R, IL-4R, IL-6R on peripheral blood lymphocytes in systemic lupus erythematosus and correlation with disease activity: a prospective study. Journal of clinical pathology 13 8881918
2021 IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors. Molecular medicine (Cambridge, Mass.) 12 34863091
2017 High expression of IL-4R enhances proliferation and invasion of hepatocellular carcinoma cells. The International journal of biological markers 12 28665449
2014 Variations in the TNFα gene and their interactions with the IL4R and IL10 genes in relation to hand osteoarthritis. BMC musculoskeletal disorders 12 25252624
2013 IL4R and IL13 polymorphic variants and development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to HBV vaccination or infection. Vaccine 12 23462527
2016 Association of IL4 and IL4R polymorphisms with multiple sclerosis susceptibility in Caucasian population: A meta-analysis. Journal of the neurological sciences 11 27000232
1992 Histological distribution of the interleukin-4 receptor (IL4R) within the normal and pathological synovium. Revue du rhumatisme et des maladies osteo-articulaires 11 1319084
2019 A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease. Pediatric rheumatology online journal 10 31269967
1997 IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4). Investigational new drugs 10 9547670
2021 Trichuris muris infection drives cell-intrinsic IL4R alpha independent colonic RELMα+ macrophages. PLoS pathogens 9 34329367
2014 Association of the IL4R single-nucleotide polymorphism I50V with recurrent spontaneous abortion (RSA). Journal of assisted reproduction and genetics 9 24803421
2006 Common variations in the IL4R gene affect splicing and influence natural expression of the soluble isoform. Human mutation 9 16917945
1999 Functional implications for signaling via the IL4R/IL13R complex on bovine cells. Veterinary immunology and immunopathology 9 10614495
2009 A comparison of effects on reproduction and neonatal development in cynomolgus monkeys given human soluble IL-4R and mice given murine soluble IL-4R. Regulatory toxicology and pharmacology : RTP 8 19217923
2020 Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques. Scientific reports 7 33328567
2004 Genomic characterization of equine interleukin-4 receptor alpha-chain (IL4R). Veterinary immunology and immunopathology 7 14741137
1995 IL-4R alpha and gamma chain expression in LPS- and IL-4-stimulated MONO-MAC-6 cells. Leukemia 7 7532769
2011 Asthma-related SNP in FCER2 is associated with increased expression of IL-4R on human B cells. International journal of immunogenetics 6 22059556
2025 Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM. Cell genomics 5 40043711
2014 PAR-2, IL-4R, TGF-β and TNF-α in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis. Experimental and therapeutic medicine 5 25009615
2007 Expression and structure of interleukin 4 receptor (IL-4R) complex in human invasive pituitary adenomas. Neuroscience letters 5 17398005
2025 Mechanism of Qingjie Fuzheng Granules in inhibiting colitis associated colorectal cancer by regulating TLR4 and IL-4R mediated macrophage polarization. Journal of ethnopharmacology 4 39978444
2024 Long non-coding RNA LBX2-AS1 activates IL4R to promote glioblastoma metastasis and angiogenesis by binding to the transcription factor NFKB1. Folia neuropathologica 4 39045789
2022 Interleukin-3 stabilizes CD124/IL-4α surface expression in mast cells via Tyk2 and STAT6. Immunology 4 36440951
2022 Association of the IL-4R Q576R Polymorphism with Pediatric Asthma: a meta-analysis. African health sciences 4 36910341
2021 Association of IL-4 and IL-4R Polymorphisms with Litter Size Traits in Pigs. Animals : an open access journal from MDPI 4 33920608
2014 Higher TGF-β with lower CD124 and TSLP, but no difference in PAR-2 expression in bronchial biopsy of bronchial asthma patients in comparison with COPD patients. Applied immunohistochemistry & molecular morphology : AIMM 3 24185116
2014 [Association study of bronchial asthma with polymorphisms of IL-4 and IL-4R receptor genes]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 3 24510574
2018 Polymorphism rs4787951 in IL-4R contributes to the increased risk of renal cell carcinoma in a Chinese population. Gene 2 30472377
2006 Lack of association of type 1 diabetes with the IL4R gene. Diabetologia 2 16538488
2024 A multifunctional antibody fusion protein 57103 targeting CD24, IL-4R, and αvβ3 for treating cancer and regulating the tumor microenvironment. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 1 38761419
2023 Anti-cancer activity of microbubble conjugated with Sorafenib containing liposome and IL4R-targeting peptide in kidney cancer cells. Cellular and molecular biology (Noisy-le-Grand, France) 1 38279420
2012 [Relationship of TGF-β and IL-4R gene polymorphisms with risk of classical Hodgkin lymphoma]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 1 23363793
2009 Interleukin 4 receptor alpha (IL4R) and calcium-activated chloride channel 1 (CLCA1) genes map to donkey chromosome. Hereditas 1 19712222
2026 Modulating tumor-associated macrophages through APP-CD74 blockade with IL4R-exosomes synergizes with PD-1 inhibition in gastric cancer. NPJ precision oncology 0 41882095
2025 Recognition of pivotal immune genes NR1H4 and IL4R as diagnostic biomarkers in distinguishing ovarian clear cell cancer from high-grade serous cancer. Frontiers in molecular biosciences 0 40656893
2024 IL-4R and CXCR2 Contribute to Downregulating Neutrophil-Mediated Response in the Early Stage of Fungal Extract-Induced Allergic Airway Inflammation. Biomedicines 0 39767651
2020 Polymorphisms of IL-4 and IL-4R are associated to some demographic characteristics of differentiated thyroid cancer patients but are not determinants of risk in the Brazilian population. Endocrine 0 32902809
2015 [Correlations of IL-4R gene polymorphism and serum IgE levels with asthma predictive index]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 26695670
2003 Coordinated regulation of the promoter and enhancer regions of human CD23 gene by signal through IL-4R and CD40, and the role of Ku70/80 in the enhancer activity. Journal of medical and dental sciences 0 12968637
1998 Function of the human interleukin 4 receptor (IL-4R)-derived acidic motif revealed by cytoplasmic domain chimeras of the IL-4R alpha chain and the IL-2R beta chain. Cytokine 0 9619370

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