Affinage

IL4R

Interleukin-4 receptor subunit alpha · UniProt P24394

Length
825 aa
Mass
89.7 kDa
Annotated
2026-04-28
96 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL4R encodes the IL-4Rα chain, the shared ligand-binding subunit of the type I (IL-4Rα/γc) and type II (IL-4Rα/IL-13Rα1) receptor complexes that transduce IL-4 and IL-13 signals across hematopoietic and non-hematopoietic cell types (PMID:9013879, PMID:9301536, PMID:15331327). Discrete cytoplasmic domains couple to distinct downstream pathways: Y497 and Y713 mediate anti-apoptotic signaling, the first conserved tyrosine (Y1) activates PI3K/mTOR to drive G2/M cell-cycle progression, and the ID-1 region signals through STAT5 for S-phase entry independent of cytoplasmic tyrosines, while the canonical output is JAK1-dependent STAT6 phosphorylation (PMID:9670964, PMID:16210622). Disease-associated coding variants alter pathway output—the R576 gain-of-function variant recruits GRB2 to activate ERK→IL-6→STAT3 signaling, reprogramming Tregs toward a TH17 fate in asthma, while the somatic I242N transmembrane mutation drives constitutive JAK-STAT activation in primary mediastinal large B-cell lymphoma (PMID:27479084, PMID:29467182). Beyond canonical immunity, IL-4Rα on smooth muscle cells controls intestinal contractility during helminth infection, on inhibitory neurons mediates T-cell-derived IL-4 effects on synaptic plasticity and episodic memory, and its surface expression is regulated post-transcriptionally by glucocorticoids, intronic SNP-dependent alternative splicing, and IGF2BP3-mediated mRNA destabilization (PMID:20360135, PMID:34793707, PMID:9847438, PMID:16917945).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 High

    Establishing the chromosomal location of IL4R (16p11.2–12.1) provided the foundation for subsequent genetic and functional studies of the receptor.

    Evidence In situ hybridization and somatic cell hybrid Southern blotting in human and interspecific backcross in mouse

    PMID:1679753

    Open questions at the time
    • No protein-level characterization or signaling data at this stage
  2. 1997 High

    Demonstrating that IL-4Rα and IL-13Rα1 co-expression reconstitutes a high-affinity IL-4/IL-13 receptor resolved how IL-13 and IL-4 share a common signaling chain and compete for receptor binding.

    Evidence Receptor reconstitution in CHO cells with radioligand binding (Kd ~30 pM for IL-13) and STAT6 EMSA; antibody blockade and phosphorylation assays in endothelial cells

    PMID:9013879 PMID:9301536

    Open questions at the time
    • Stoichiometry and structural basis of the heterodimer not determined
    • Contribution of γc versus IL-13Rα1 chains to differential signaling not yet dissected
  3. 1998 High

    Mapping individual cytoplasmic tyrosines to discrete functions (Y497/Y713 for anti-apoptosis; acidic domain for proto-oncogene induction) established that the IL-4Rα tail is a modular signaling scaffold rather than a single-output transducer.

    Evidence Domain transplant chimeras and Y→F mutagenesis in 32D cells; IL-2Rβ/IL-4Rα domain-swap chimeras in BA/F3 cells

    PMID:9619370 PMID:9670964

    Open questions at the time
    • Kinase(s) directly phosphorylating Y497 and Y713 not identified
    • Downstream effectors coupling these tyrosines to survival signals not mapped
  4. 1998 High

    Discovering that glucocorticoids downregulate IL-4Rα through two distinct posttranscriptional mechanisms revealed that receptor abundance is actively controlled beyond transcription.

    Evidence Nuclear run-on, Northern blot, mRNA stability assays, and GR antagonist (RU486) reversal in PMA- and IL-4-stimulated cells

    PMID:9847438

    Open questions at the time
    • Identity of the mRNA destabilizing factor(s) recruited by GR unknown
    • Translational/posttranslational mechanism for IL-4-induced receptor regulation not molecularly defined
  5. 1999 High

    Testing the atopy-associated Q576R variant and finding no enhanced IL-4 signaling in multiple assays challenged the assumption that this variant is a direct gain-of-function for canonical STAT6 output.

    Evidence WT versus Q576R IL-4Rα cDNA expressed in murine cells, with phosphorylation, EMSA, proliferation, apoptosis, and CD23 readouts

    PMID:10201973

    Open questions at the time
    • Did not test non-canonical pathways (e.g., ERK, IL-6) that were later implicated
    • Murine cellular context may not capture human-specific signaling differences
  6. 2001 High

    Showing that IL-13 can drive airway hyperreactivity through STAT6 independently of IL-4Rα revealed an alternative IL-13 signaling route, refining the model that all IL-13 effects require IL-4Rα.

    Evidence Adoptive T-cell transfer into IL-4Rα−/− versus STAT6−/− mice with airway hyperreactivity and eosinophilia readouts

    PMID:11466392

    Open questions at the time
    • Identity of the IL-4Rα-independent receptor complex mediating IL-13/STAT6 signaling not established
    • Whether this pathway operates outside the lung not tested
  7. 2004 High

    Discriminating type I (IL-4Rα/γc) from type II (IL-4Rα/IL-13Rα1) receptor function using an IL-13 mutant antagonist and showing that the I50V variant alters STAT6 transcriptional amplitude without changing Th2 differentiation revealed selective modularity of receptor-complex outputs.

    Evidence Receptor-specific cell lines with competitive binding and STAT6 phosphorylation; I50 vs V50 variant comparison with STAT6 reporters and Th2 assays

    PMID:15331327 PMID:15383584

    Open questions at the time
    • Structural basis of how I50V variant augments STAT6 activation not solved
    • Whether type II-selective antagonism has distinct downstream transcriptional consequences not profiled
  8. 2005 High

    Demonstrating that a tyrosine-less IL-4Rα tail still drives S-phase entry via the ID-1/STAT5 axis, while Y1 engages PI3K/mTOR for G2/M completion, resolved how IL-4 couples receptor domains to distinct cell-cycle checkpoints.

    Evidence Multiple cytoplasmic tyrosine mutant constructs in primary activated T cells, BrdU incorporation, rapamycin sensitivity, p70S6K phosphorylation

    PMID:16210622

    Open questions at the time
    • Direct binding partner linking ID-1 to STAT5 not identified
    • Whether mTOR-dependent G2/M regulation operates in non-T cells unknown
  9. 2006 High

    Bone marrow chimera and splicing studies collectively showed that IL-4Rα function is partitioned by cell type (hematopoietic for macrophage polarization and survival vs. non-hematopoietic for granuloma/fibrosis) and that soluble IL-4Rα levels are governed by intronic SNP-dependent alternative splicing.

    Evidence Reciprocal BM chimeras in IL-4Rα−/− mice with S. mansoni infection; minigene splicing assays and human mRNA quantification for intronic SNPs; IL-4Rα−/− Nippostrongylus model for IL-10/Th2 dependence

    PMID:16917945 PMID:16940042 PMID:18354220

    Open questions at the time
    • How splicing factor SRp20/YT521-B are themselves regulated in disease contexts not known
    • Quantitative contribution of soluble vs. membrane IL-4Rα to pathway output in vivo not measured
  10. 2010 High

    Cell-type-specific conditional knockout in smooth muscle cells demonstrated that IL-4Rα directly controls intestinal hypercontractility needed for helminth expulsion, extending IL-4Rα function beyond immune cells.

    Evidence SM-MHC-Cre × IL-4Rαfl/flox mice with S. mansoni infection, intestinal contractility assays, egg counts, survival

    PMID:20360135

    Open questions at the time
    • Downstream contractile effectors activated by IL-4Rα in smooth muscle not characterized
    • Whether type I or type II receptor mediates the smooth muscle response not determined
  11. 2011 High

    Establishing that IL-4Rα activates STAT6/Akt/MAPK in rhabdomyosarcoma to promote proliferation and suppress myogenic differentiation, with anti-IL-4Rα antibody reducing metastases in vivo, linked IL-4Rα signaling to solid tumor biology.

    Evidence IL-4/IL-13 stimulation of RMS lines with Western blot for STAT6/Akt/MAPK/MyoD; anti-IL-4Rα antibody in genetically engineered mouse ARMS model

    PMID:21536546

    Open questions at the time
    • Relative contributions of STAT6 versus Akt versus MAPK to metastatic phenotype not dissected
    • Whether IL-4Rα signals cell-autonomously versus through tumor microenvironment not fully resolved
  12. 2016 High

    Identifying that the R576 variant recruits GRB2→ERK→IL-6→STAT3 to reprogram Tregs toward TH17 provided the first mechanistic explanation for how a coding variant in IL-4Rα exacerbates asthma through a non-canonical signaling axis.

    Evidence R576 knock-in mice with Treg-specific conditional KOs of IL6ra and Rorc; GRB2 co-IP with IL-4Rα R576; anti-IL-6 rescue

    PMID:27479084

    Open questions at the time
    • Whether GRB2 recruitment occurs at a specific phosphotyrosine or non-tyrosine motif not mapped
    • Generalizability to human Treg cells not directly shown
  13. 2018 High

    Discovery that somatic I242N transmembrane mutations constitutively activate JAK-STAT in primary mediastinal large B-cell lymphoma established IL-4Rα as a bona fide oncogenic driver when mutated in its transmembrane domain.

    Evidence PMBCL sequencing, functional assays of I242N mutant, JAK-STAT signaling, xenotransplantation growth advantage

    PMID:29467182

    Open questions at the time
    • Structural mechanism by which I242N causes ligand-independent dimerization/activation not solved
    • Whether other transmembrane mutations have similar effects not systematically tested
  14. 2021 High

    Conditional knockout of IL-4Rα on inhibitory neurons impaired episodic memory and long-term potentiation, revealing an unexpected neuroimmune role for IL-4Rα in synaptic plasticity independent of peripheral immunity.

    Evidence Vgat-Cre × IL-4Rαfl/flox mice, contextual fear conditioning, LTP recordings, snRNA-seq, T-cell adoptive transfer

    PMID:34793707

    Open questions at the time
    • Downstream signaling pathway in neurons (STAT6 vs. other) not fully characterized
    • Whether IL-4Rα signals through type I or type II receptor in GABAergic neurons not determined
  15. 2022 Medium

    Showing that IL-3 maintains surface IL-4Rα via Tyk2/STAT6/HSP90 on mast cells identified a cytokine-driven feedforward loop that primes IL-4 responsiveness on effector cells.

    Evidence Pharmacological inhibition of Tyk2, STAT6, and HSP90 in mast cells with surface IL-4Rα flow cytometry

    PMID:36440951

    Open questions at the time
    • Whether HSP90 acts on IL-4Rα protein folding/stability or transcription not resolved
    • Single lab finding with pharmacological inhibitors only

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis for ligand-independent activation by transmembrane mutations, the identity of the IL-4Rα-independent IL-13/STAT6 pathway component, and the signaling logic by which IL-4Rα in neurons regulates synaptic gene programs.
  • No crystal structure of full-length IL-4Rα in a signaling-competent complex
  • IL-4Rα-independent IL-13 receptor component never identified
  • Neuronal downstream signaling cascade not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3
Partners
GRB2IGF2BP3IL13RA1IL2RGJAK1STAT5STAT6
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 IL-4Rα and IL-13Rα1 together reconstitute a functional high-affinity IL-4/IL-13 receptor complex: CHO cells co-expressing both chains bound IL-13 with Kd ~30 pM and allowed cross-competition of IL-13 and IL-4, whereas each chain alone could not activate STAT6; IL-4Rα alone did not bind IL-13. Receptor reconstitution in CHO cells (co-expression), radioligand binding, electrophoretic mobility shift assay (EMSA) for STAT6 activation FEBS letters High 9013879
1997 IL-13 signals through IL-4Rα in human endothelial cells: a neutralizing anti-IL-4Rα monoclonal antibody blocked IL-13-induced MCP-1 expression; IL-13 and IL-4 both caused rapid tyrosine phosphorylation of immunoprecipitated IL-4Rα and activated STAT6. Neutralizing antibody blockade, immunoprecipitation with phosphotyrosine detection, EMSA for STAT6 Immunology High 9301536
1998 Tyrosine residues Y497 and Y713 within the cytoplasmic tail of IL-4Rα are required for IL-4-mediated protection from apoptosis; the domain containing the STAT6-docking tyrosines suppresses this protection. Transplantation of Y497 or Y713 domains to a truncated IL-2Rβ partially conferred protection, and Y→F mutation abolished it. Cytoplasmic domain transplant chimeras, site-directed mutagenesis (Y→F), apoptosis assays in 32D cells Journal of immunology High 9670964
1998 Glucocorticoids (dexamethasone) down-regulate IL-4Rα expression by two distinct posttranscriptional mechanisms: (1) PMA-induced IL-4Rα expression is suppressed by decreasing mRNA half-life; (2) IL-4-induced IL-4Rα expression is suppressed at the translational or posttranslational level without changing mRNA stability or transcription rate. The effect is glucocorticoid-receptor-dependent (reversed by RU486). Northern blot, nuclear run-on transcription assay, flow cytometry, mRNA stability assay, GR antagonist (RU486) The Journal of allergy and clinical immunology High 9847438
1999 The allergy-associated IL-4Rα mutation Q576R (Q551R in some numbering) does not significantly alter IL-4-induced tyrosine phosphorylation, STAT6 DNA-binding, proliferation, apoptosis protection, or CD23 induction compared to wild-type receptor in murine cells expressing human IL-4Rα cDNA, indicating this variant does not directly enhance IL-4 signal transduction. Transfection of WT and mutant (Q576R, Y575F) human IL-4Rα cDNA in murine cells, phosphorylation assays, EMSA, proliferation and apoptosis assays, CD23 induction Journal of immunology High 10201973
2001 IL-13-induced airway hyperreactivity and eosinophilia can occur independently of IL-4Rα but requires STAT6, revealing a novel IL-13 signaling pathway through a different receptor component that involves STAT6 without IL-4Rα. Adoptive transfer of IL-13+/+ or IL-13−/− CD4+ T cells into WT and IL-4Rα−/− or STAT6−/− mice, airway hyperreactivity and eosinophilia readouts Journal of immunology High 11466392
2004 The IL-4Rα variant encoding isoleucine at position 50 (I50) acts as a gain-of-function allele relative to V50 for STAT6-dependent transcriptional activity, but this enhanced STAT6 signaling does not increase Th2 differentiation efficiency or IL-4-mediated repression of Th1 development. Transfection of I50 vs V50 variant IL-4Rα in primary T cells, STAT6 reporter assays, Th2 differentiation assays Journal of immunology Medium 15383584
2004 IL-13E13K (an IL-13 mutant antagonist) inhibits IL-4 binding and STAT6 phosphorylation in cells expressing the type II IL-4R (IL-4Rα/IL-13Rα1 heterodimer) but not type I IL-4R (IL-4Rα/γc), because Glu13 of IL-13 contacts IL-4Rα and its mutation to lysine prevents IL-13Rα1/IL-4Rα heterodimerization. Receptor-specific cell lines, competitive binding assay, STAT6 phosphorylation assay, protein synthesis inhibition assay Cellular immunology High 15331327
2005 In primary T cells, IL-4Rα lacking all cytoplasmic tyrosines can still signal for STAT5 phosphorylation and S-phase entry via an intact ID-1 region; Y1 (first conserved tyrosine) activates the PI3K/mTOR pathway to promote G2/M progression, and rapamycin blocks cell-cycle completion but not S-phase entry downstream of IL-4Rα. Cytoplasmic tyrosine mutant IL-4Rα constructs in primary activated T cells, BrdU incorporation, rapamycin treatment, p70S6K phosphorylation assay Journal of immunology High 16210622
2006 IL-4Rα/STAT6 signaling in bone marrow-derived (hematopoietic) cells is both necessary and sufficient for protection against acute schistosomiasis by enabling alternatively activated macrophage generation and suppressing IL-12/TNF/IFN-γ-driven inflammation; IL-4Rα signaling in non-hematopoietic cells governs granuloma size and fibrosis but not survival. Bone marrow chimera experiments with IL-4Rα−/− and WT donors/recipients, cytokine measurements, pathology scoring Journal of immunology High 18354220
2006 IL-4Rα signaling is required for IL-10 production by an IL-10+ Th2 subpopulation, and IL-10 is the key IL-4Rα-dependent factor that suppresses Th1 responses to maintain Th2 dominance during nematode infection. IL-4Rα−/− mice infected with Nippostrongylus brasiliensis, cytokine profiling, Th1 neutralization rescue experiments International immunology Medium 16940042
2006 Common intronic SNPs in IL4R (c.912-1003A>G, c.912-833T>C, c.912-630A>G, c.912-577A>G) affect alternative splicing of IL4R: minor alleles at these linked SNPs reduce exon 8 inclusion, decreasing expression of the soluble IL-4Rα isoform. This was demonstrated with an IL4R minigene construct and confirmed in human mRNA samples; splicing factors SRp20 and YT521-B modulate this. Minigene splicing assay, mRNA quantification in human samples, splicing factor overexpression Human mutation High 16917945
2010 IL-4Rα responsiveness in smooth muscle cells (non-hematopoietic) is required for IL-4/IL-13-mediated intestinal hypercontractility, which in turn promotes S. mansoni egg expulsion and host survival during acute schistosomiasis; smooth muscle cell-specific IL-4Rα deletion increased susceptibility independently of Th2 cytokine levels. Conditional knockout mice (SM-MHC-Cre × IL-4Rαfl/flox), S. mansoni infection, intestinal contractility assay, egg counts, survival American journal of physiology. Gastrointestinal and liver physiology High 20360135
2011 IL-4Rα signaling in rhabdomyosarcoma activates STAT6, Akt, and MAPK pathways; IL-4 and IL-13 stimulation promotes tumor cell proliferation and downregulates MyoD and Myogenin (myogenic differentiation factors); neutralizing anti-IL-4Rα antibody in a mouse ARMS model significantly reduced lymph node and pulmonary metastases. In vitro IL-4/IL-13 stimulation of human RMS lines (RD, Rh30) and primary mouse ARMS cells; Western blotting for STAT6, Akt, MAPK, MyoD, Myogenin; in vivo neutralizing antibody in genetically engineered mouse model Clinical cancer research High 21536546
2016 An asthma-associated IL-4Rα variant (R576) promotes conversion of induced Treg cells to TH17-like cells 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 IL-4 or IL-13) prevented exacerbated airway inflammation in Il4ra(R576) knock-in mice. R576 knock-in mice, Treg-specific conditional knockouts (IL6ra, Rorc, IL-4, IL-13), GRB2 co-immunoprecipitation, ERK/STAT3 pathway analysis, anti-IL-6 antibody treatment Nature medicine High 27479084
2018 Somatic IL4R mutations (most commonly I242N in the transmembrane domain) in primary mediastinal large B-cell lymphoma (PMBCL) are gain-of-function, causing constitutive JAK-STAT pathway activation, upregulation of downstream cytokine expression, and growth advantage in vivo in a mouse xenotransplantation model. Sequencing of primary PMBCL cases and cell lines, functional assays of I242N mutant IL4R, JAK-STAT signaling assays, xenotransplantation mouse model Blood High 29467182
2021 IL-4Rα on GABAergic (inhibitory) neurons mediates T cell (via IL-4) effects on synaptic plasticity and episodic memory: IL-4Rα knockout specifically in inhibitory neurons impaired contextual fear memory, and snRNA-seq implicated IL-4-driven regulation of synaptic function and plasticity pathways. Inhibitory neuron-specific IL-4Rα conditional knockout (Vgat-Cre), contextual fear memory assay, long-term potentiation recording, snRNA-seq, T-cell adoptive transfer in SCID and IL-4 KO backgrounds Neuron High 34793707
1991 The IL4R gene was mapped to human chromosome 16p11.2–16p12.1 by in situ hybridization and mouse-human somatic cell hybrid Southern blotting, and the mouse homolog was positioned in the distal region of chromosome 7. In situ hybridization, Southern blot of somatic cell hybrid panel, interspecific backcross analysis Genomics High 1679753
2017 IL-4Rα knockdown in hepatocellular carcinoma cell lines abolishes IL-4-induced activation of JAK1/STAT6 and JNK/ERK1/2 signaling pathways and results in enhanced apoptosis, impaired proliferation, and reduced invasion. siRNA knockdown of IL-4R in HCC cell lines, Western blot for JAK1/STAT6 and JNK/ERK1/2, flow cytometry for apoptosis and cell cycle, invasion assays The International journal of biological markers Medium 28665449
2021 IL-4/IL-4Rα type I receptor signaling in osteoclast precursors (OCPs) activates ERK pathway to promote OCP proliferation during early bone metastasis of colorectal cancer; IL-4 is supplied by neutrophils in bone marrow. ERK antagonist Ravoxertinib inhibited OCP proliferation and prevented bone destruction. BrdU assay for OCP proliferation, IL-4 deficiency mice, tumor conditioned medium stimulation, ERK pathway Western blot, ERK inhibitor Ravoxertinib in vivo Molecular medicine Medium 34863091
1998 The acidic motif of IL-4Rα cytoplasmic domain can functionally substitute for the acidic region (A-region) of IL-2Rβ to support c-junB and c-fos induction, while the haematopoietin box1 (S-region equivalent) of IL-4Rα cannot substitute for the S-region of IL-2Rβ for growth signaling; demonstrated by cytoplasmic domain chimeras. Chimeric receptor construction (IL-2Rβ/IL-4Rα domain swaps), stable transfection in BA/F3 cells, proto-oncogene induction assays, IL-2-driven proliferation assay Cytokine Medium 9619370
2022 IL-3 maintains surface IL-4Rα (CD124) expression on mast cells through a Tyk2/STAT6/HSP90-dependent mechanism; inhibition of Tyk2, STAT6, or HSP90 impaired IL-3-induced IL-4Rα upregulation. Mast cells in this context do not express IL-13Rα1. Pharmacological inhibition of Tyk2, STAT6, HSP90 in mast cells; surface IL-4Rα flow cytometry; Western blot for signaling molecules Immunology Medium 36440951
2025 IGF2BP3 (an RNA-binding protein) directly binds IL4R and IL13RA1 mRNAs, decreasing their stability; depletion of IGF2BP3 increased IL4R and IL13RA1 mRNA half-life, elevated IL-4Rα and IL-13Rα1 surface expression, and enhanced IL-13/IL-4-induced STAT6 phosphorylation in airway epithelial cells. RNA-binding protein immunoprecipitation (RIP), mRNA stability (half-life) assay, surface receptor flow cytometry after IGF2BP3 knockdown, STAT6 phosphorylation assay, RNA-seq bioRxivpreprint 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 154 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 88 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 48 21536546
2010 Immunomodulation with IL-4R alpha antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease. Journal of immunology (Baltimore, Md. : 1950) 46 20861354
2018 Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to constitutive JAK-STAT signaling activation. Blood 44 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 38 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
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
2020 IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory. Scientific reports 21 33020569
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
2005 Sequence motifs in IL-4R alpha mediating cell-cycle progression of primary lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 20 16210622
2017 Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A Meta-Analysis. Disease markers 19 28392616
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
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
2018 Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization: Results from Two Population-Based Birth Cohort Studies. Scientific reports 12 29459738
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
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
2021 Trichuris muris infection drives cell-intrinsic IL4R alpha independent colonic RELMα+ macrophages. PLoS pathogens 8 34329367
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
2021 Association of IL-4 and IL-4R Polymorphisms with Litter Size Traits in Pigs. Animals : an open access journal from MDPI 4 33920608
2022 Association of the IL-4R Q576R Polymorphism with Pediatric Asthma: a meta-analysis. African health sciences 3 36910341
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
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 A multifunctional antibody fusion protein 57103 targeting CD24, IL-4R, and αvβ3 for treating cancer and regulating the tumor microenvironment. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 0 38761419
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