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Symbol IL4 contributors: mct/pgu - updated : 09-03-2017
HGNC name interleukin 4
HGNC id 6014
Corresponding disease
APY10 predisposition to eczema and asthma, atopy 10
Location 5q31.1      Physical location : 132.009.372 - 132.018.368
Synonym name
  • B-cell stimulatory factor 1
  • lymphocyte stimulatory factor 1
  • B cell growth factor 1
  • binetrakin
  • pitrakinra
  • Synonym symbol(s) BSF1, IL-4, BCGF1, BCGF-1, MGC79402
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 8.70 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure the coordinate regulator (LCR) of IL4, IL3 and IL5 is a 0.4kb sequence which is located in the intergenic region between IL4 and IL13 (Loots 00)
    MAPPING cloned Y linked N status confirmed
    Map see IRF1
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 921 17.5 153 - 1995 7806280
    3 splicing 873 15.7 137 - 1995 7806280
    lacking exon 2
    - splicing - - - - 2011 21285395
  • lacking the region encoded by the second exon
  • in contrast to IL4, IL4D2 did not induce eosinophilia or goblet cell hyperplasia
  • promotes lymphocytic inflammation, and the effects of IL4D2 are not mediated by endogenous IL4
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   moderately
     tonsils   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium  
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
  • a 24 aa signal peptide (2,5kDA)
  • conjugated GlycoP
    isoforms Precursor a 129 amino acids mature peptide (15,0 kda)
    interspecies ortholog to C.elegans y43f8b.12
  • interleukin, IL-4/IL-13 family
  • CATEGORY immunity/defense , signaling cytokine
    basic FUNCTION
  • important switch factor directing Ig-E synthesis
  • T cell and mast cell growth factor activities
  • potent modulator of ion transport in the bronchial epithelium and of ion composition of airway surface fluid
  • inhibition of matrix metalloproteinas-3 (MMP-3) synthetis in fibroblasts
  • involved in excessive deposition of extracellular matrix (EMC) proteins in giant papillae
  • directing germinal center-B cells to differentiate into memory B cells
  • Th2-promoting cytokine IL4 played a permissive role that superseded Treg function, thereby allowing the development of allergic inflammation
  • with its STAT6-signalling pathway are critical for the expression of Th2 effector immune responses in peripheral tissues such as the skin, lung and gut
  • important immune regulatory protein that possesses potent anti-osteoclastogenic properties, and does so via the transcription factor STAT6
  • IL4 and IL13 prime the migrational response of haemopoietic progenitor cells to CXCL12 by enhancing the incorporation of CXCR4 into lipid rafts
  • plays a critical role in higher functions of the normal brain, such as memory and learning
  • IL13 and IL4 can uniquely affect the expression of particular genes such as DUSP1 and TIMP33 and do so through different Jaks
  • IL4 exerts its proliferative actions via IL4R in hepatocytes, and eosinophil-derived IL4 stimulates hepatocyte proliferation in regenerating liver
  • IL4 and IL4 receptor expression is dispensable for the development and function of natural killer T cells
  • plays a central role in the orchestration of Type 2 immunity
  • during T cell activation in the lymph node, IL4 promotes Th2 differentiation and inhibits Th1 generation
  • attenuates Th1-associated chemokine expression and Th1 trafficking to inflamed tissues and limits pathogen clearance
  • IL4 up-regulation of IL19 in keratinocytes, which may play an important role in AD pathogenesis
  • IL4 and melatonin inhibited inflammation and angiogenesis triggered by high glucose and IL1B
  • induction of IL7R expression on Dendritic cells is critical for Thymic stromal lymphopoietin (TSLP) responsiveness and IL4 can upregulate IL7R on Dendritics cells
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    text differentiation and proliferation of B cells, T cells and mast cells
  • IL4 pathway of proliferation may have developed as an alternative to CSF1 to increase resident macrophages numbers without coincident monocyte recruitment
  • a component
    small molecule
  • activating STAT6
  • regulating CCR5 and CD4 expression and HIV1 replication in macrophages and microglia
  • MINA, is an IL4 repressor, controling T helper type 2 bias
  • IL4, IL9, IL13 may increase CLCA1 expression in cystic fibrosis but may not have a significant effect on mucus expression
  • CCL26 is a functional ligand for CCR3 and abundantly produced by IL4-/IL13-stimulated vascular endothelial cells
  • novel role of IL4/IL13-induced DUOX1 expression in making a positive feedback loop for IL4/IL13 signaling in keratinocytes
  • IL4 inhibits osteoclast formation by inhibiting TNFSF11 induction of NFATC1 via STAT6 as an early event, in addition to its suppression of other signaling pathways
  • IRF4 activates IL2 and IL4 promoters in cooperation with REL
  • role of posttranslational modification of MAF in IL4 production and Th cell-mediated autoimmune diseases
  • IL4 downregulated in a STAT6-dependent manner the memory-specific expression of KLRK1, thereby increasing the activation threshold of memory CD8 T cells
  • thyroid hydrogen peroxide production is enhanced by the Th2 cytokines, IL4 and IL13, through increased expression of the DUOX2 and its maturation factor DUOXA2
  • while IL4 inhibits and activates different sets of lysosomal genes, STAT6 mediates only the activating effects of IL4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL4
  • ICOS costimulation-dependent translational control may ensure targeted delivery of IL4 to cognate B cells during T-B collaborations in the germinal center
  • key role for KLF13 in the expression of IL4 in CD4(+) T cells
  • KLF13 cooperates with MAF to regulate IL4 expression in CD4+ T cells
  • IL4 was able to inhibit BCL2L11 upregulation and prevent cell death, and downmodulation of BCL2L11 by IL4 occurred in a posttranscriptional manner
  • IL4 increases the binding of STAT6 to its response elements in the IL19 promoter
  • IL4 is essential for the production of IL31, whereas TGFB1 significantly suppresses IL31 expression at the mRNA and protein levels
  • IL4 cooperates likely with IL5 to promote eosinophil differentiation
  • IL4 and IL13, are critical factors for the induction of CCL26 in the pancreas
  • IL4 and IL21 cooperate to induce the high BCL6 protein level required for germinal center formation
  • DUOX1 regulates primary B cell function under the influence of IL4 through BCR-mediated generation of hydrogen peroxide
  • cell & other
    activated by JUNB, a transcriptional activator of various cytokine genes, such as IL2, IL4, and IL10
    inhibited by ICAM1 in CD4(+) T cells
    repressed by PTPN6 that is an essential negative regulator of IL4 signaling in T lymphocytes
    Other regulated by MAF a potent transactivator
    of the IL4 gene in Th2 cells
    regulated by MAPK14 (regulates IL4 production by mRNA stabilization, and TCR stimulation phosphorylates MAPK14, partially through the calcium-dependent pathway)
    corresponding disease(s) APY10
  • to thromboembolic strocke
  • to diabetic peripheral neuropathy (DPN)
  • Variant & Polymorphism repeat , other
  • C582T is a predictor of thromboembolic strocke
  • intron 3 VNTR polymorphism of the IL4 gene plays an important role in the occurrence of DPN
  • Candidate gene
    Therapy target
    transgenic mice that inappropriatly expressed IL4 under the direction of the proximal promoter for the lymphocyte-specific protein tyrosine kinase gene (lck/IL4) developed severe osteoporosis