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FLASH GENE
Symbol IL10 contributors: mct - updated : 17-11-2017
HGNC name interleukin 10
HGNC id 5962
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoietic    
Connective    
Lymphoid    
cells
SystemCellPubmedSpeciesStageRna symbol
 mast cell
Blood/Hematopoieticneutrophil
Lymphoid/ImmuneB cell
Lymphoid/Immunemacrophage
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , dimer
HOMOLOGY
Homologene
FAMILY
  • interleukin family
  • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text produced by neutrophils during sepsis
    basic FUNCTION
  • cytokine synthesis inhibitory factor
  • costimulator of proliferation and differentiation of B, T, mast cell
  • exerts potent anti-inflammatory actions and modulates matrix metalloproteinase expression
  • chemotactor for CD8+ T cells
  • involved in regulating the intensity and duration of the immune response
  • playing an important role in the development of infectious disease
  • directing germinal center-B cells to differentiate into plasma cells
  • IL10 signaling plays a non-critical role in suppression of inflammatory mediators, resolution of the inflammatory response, and fibrous tissue deposition following myocardial infarction
  • important immunoregulatory cytokine that functions to downregulate immune responses
  • regulates ADAM17, involving a TIMP3 dependent and independent mechanism)
  • IL10 and IL13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE)
  • inhibits transcription elongation of the human TNF gene in primary macrophages
  • multi-functional cytokine that plays a crucial role in maintaining the balance between immunity and tolerance
  • anti-inflammatory interleukin-10 (IL10), endowed Treg cells with the ability to suppress pathogenic Th17 cell responses
  • prevents apoptosis of brain endothelium during bacteremia
  • IL10 and IL22 are crucial regulators of inflammation during immune responses, and IL10 functions to prevent excessive inflammation by acting on immune cells
  • critical anti-inflammatory cytokine, the deficiency of which leads to spontaneous autoimmunity
  • T cell specific actions of IL10 can support autoimmune inflammation, and this appears to result from an overall increase in the long term fitness of pathologic T cells
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS immunity/defense
    text antimicrobial immune response
    PATHWAY
    metabolism
    signaling signal transduction
    cell to cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • upregulating CCR5, CD4 expression and HIV1 replication in human macrophages and microglia
  • interaction with IRF4 (regulates IL10 gene expression in CD4(+) T cells through differential nuclear translocation)
  • is negatively regulated at the transcriptional level by the STAT3 (signal transducer and activator of transcription 3)-activating anti-inflammatory cytokine IL10
  • can have opposite effects on MARCH1 regulation in different cell types
  • HDAC3 is involved in histone deacetylation of the IL12B promoter by IL10
  • ABCA1 promotes the secretion of IL10, an anti-inflammatory cytokine critical for inflammation resolution
  • IL10 activates TLR4 and requires MYD88 for cardiomyocyte survival
  • IL10 modulates SLC6A4 activity and expression in intestinal epithelial cells, depending on its extracellular conditions
  • ID2 acts to repress the TCF3-mediated trans-activation of the Il10 locus
  • IL27/NFIL3 signalling axis is a key regulator of effector T-cell responses via induction of HAVCR2, IL10 and T-cell dysfunction
  • MEF2D is a critical regulator of IL10 gene expression that negatively controls microglia inflammation response and prevents inflammation-mediated cytotoxicity
  • MAP2K1 is required for TLR4 mediated ERK activation and in turn regulates the production of IL10 and IL12A
  • SYK negatively regulates TLR4-mediated production of IFNB1 and IL10 and promotes inflammatory responses in dendritic cells through divergent regulation of downstream PI3K-AKT1 and NFKB1 signaling pathways
  • RBPJ binds and trans-activates the IL23R promoter and induces IL23R expression and represses anti-inflammatory IL10 production in Th17 cells
  • ETV5 plays a crucial role in regulating IL10 production in Th2 cells by facilitating the binding of IL10-inducing transcription factors at the IL10 locus
  • CRP may be a potent inducer of the anti-inflammatory cytokine IL10
  • GPR39 exhibits likely an anti-inflammatory activity by enhancing IL10 production from macrophages
  • cell & other
    REGULATION
    activated by JUNB, a transcriptional activator of various cytokine genes, such as IL2, IL4, and IL10
    CAMK2B that specifically activates IL10 promoter activity
    MRF2A (overexpression of MEF2A enhanced by 2.5-fold IL10 promoter activity)
    IFNB1, that stimulates IL10 production by activating the JAK1- and PI3K-signaling pathways
    repressed by PBRM1 which is a repressor of IL10 transcription in Th2 cells, suggesting that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     loss of function
    loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD)
    tumoral     --over  
    in diffuse large B-cell lymphoma, patients with high serum IL10 had shorter event-free survival (EFS) than patients with low levels
    constitutional     --over  
    DNA hypomethylation leads to IL10 and IL13 overexpression in systemic lupus erythematosus patients
    constitutional     --low  
    is associated with risk of Behçet disease (BD)
    Susceptibility
  • to hepatocellular carcinoma (HCC)
  • to acute myocardial infarction
  • to Wegener's granulomatosis
  • to sudden infant death with infectious cause
  • to SLE systemic lupus erythematosus
  • to severe malarial anemia
  • to leprosy
  • Variant & Polymorphism SNP , repeat , other
  • CA repeat in IL10 associated with WG
  • IL10 HT2 accelerates progression of chronic hepatitis B virus infection especially to HCC development
  • 1082GG genotype protecting against myocardial infarction
  • CA repeat polymorphism IL-10.G, associated with Wegener's granulomatosis
  • alleles G21/G22 and G21/G23, associated with infectious cause of sudden infant death
  • SNP 819T is associated with leprosy susceptibility
  • haplotypes of IL10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL10 production
  • rs3024505 significantly associated to SLE
  • Candidate gene
    Marker
  • may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy, in diffuse large B-cell lymphoma
  • Therapy target
    ANIMAL & CELL MODELS
  • IL10 deficiency affects the immune functions of dendritic cells, which may contribute to the increased severity of autoimmune diseases seen in IL-10(-/-) mice (