Homo sapiens Gene: IL10
Summary
InnateDB Gene IDBG-106270.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IL10
Gene Name interleukin 10
Synonyms CSIF; GVHDS; IL-10; IL10A; TGIF;
Species Homo sapiens
Ensembl Gene ENSG00000136634
Encoded Proteins
interleukin 10
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
IL10 expression is regulated in different immune cells has revealed some of the molecular mechanisms involved at the levels of signal transduction, epigenetics, transcription factor binding and gene activation.
IL10 is a potent anti-inflammatory cytokine that is crucial for down-regulating pro-inflammatory genes which are induced by Toll-like Receptor (TLR) signalling. It also plays a role in microRNA function, specifically its inhibitory effect on miR-155 expression in response to LPS.
IL10 is a pleiotropic cytokine released in many tissues that mediates anti-inflammatory effects. IL10 also has an immunomodulatory role by stimulating NKG2D ligand expression on macrophages, thereby rendering them susceptible to natural killer (NK) cell elimination.
IL10 contributes to antiviral innate immunity during acute infection by restricting activation-induced death in natural killer (NK) cells. Blockade of Il10 receptor during acute murine cytomegalovirus (CMV) infection markedly reduced the accumulation of cytotoxic NK cells in the spleen and lung. (Demonstrated in murine model)
IL10 has opposing functions in anti-microbial responses in its capacity to mediate protective immunity against some organisms but increase susceptibility to other infections.
IL10-mediated suppression of natural killer/dendritic cell crosstalk leads to prolonged mouse cytomegalovirus (MCMV) persistence due to poor priming of MCMV-specific T cells. (Demonstrated in mouse)
IL10 induces MIR187 to limit the expression of pro-inflammatory cytokines.
MIR145 directly targets HDAC11 to promote IL10 expression in TLR4-triggered macrophages.
HIV-1 infection of macrophages modulates host responses to co-infection with Mycobacterium tuberculosis by attenuating IL10 responses thus contributing to the pathogenesis of tuberculosis in HIV-1??infected patients.
Secreted CCNA2 (CCN1) promotes anti-inflammatory cytokine IL10 release from epithelial cells via integrin αVβ6-PKC, and this subsequently suppresses TNF, CXCL2 and neutrophil infiltration in the lungs.
MIR29A inhibits IL10-induced cytokine release by targeting JAK-STAT3 in monocytes during sepsis.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Il10 contributes to antiviral innate immunity during acute infection by restricting activation-induced death in natural killer (NK) cells. Blockade of Il10 receptor during acute murine cytomegalovirus (CMV) infection markedly reduced the accumulation of cytotoxic NK cells in the spleen and lung.
[Mus musculus] Il10 has opposing functions in anti-microbial responses in its capacity to mediate protective immunity against some organisms but increase susceptibility to other infections.
[Mus musculus] Il10-mediated suppression of natural killer/dendritic cell crosstalk leads to prolonged mouse cytomegalovirus (MCMV) persistence due to poor priming of MCMV-specific T cells.
[Mus musculus] Retinoic acid treatment enhances Tlr2-dependent Il10 production from T cells and this, in turn, potentiates T regulatory cell generation without the need for activation of antigen presenting cells.
[Mus musculus] Intestinal macrophages that constitutively produce IL10, control excessive innate immune activation and prevent tissue damage after an acute bacterial infection.
Entrez Gene
Summary The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis.[provided by RefSeq, May 2011]
Gene Information
Type Protein coding
Genomic Location Chromosome 1:206767602-206772494
Strand Reverse strand
Band q32.1
Transcripts
ENST00000367099
ENST00000423557 ENSP00000412237
ENST00000471071
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.
They are also associated with 14 interaction(s) predicted by orthology.
Experimentally validated
Total 23 [view]
Protein-Protein 11 [view]
Protein-DNA 11 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 1 [view]
DNA-RNA 0
Predicted by orthology
Total 14 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005125 cytokine activity
GO:0005141 interleukin-10 receptor binding
GO:0008083 growth factor activity
Biological Process
GO:0001818 negative regulation of cytokine production
GO:0002237 response to molecule of bacterial origin
GO:0002740 negative regulation of cytokine secretion involved in immune response
GO:0002875 negative regulation of chronic inflammatory response to antigenic stimulus
GO:0002904 positive regulation of B cell apoptotic process
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007253 cytoplasmic sequestering of NF-kappaB
GO:0007267 cell-cell signaling
GO:0007568 aging
GO:0010033 response to organic substance
GO:0010468 regulation of gene expression
GO:0014823 response to activity
GO:0014854 response to inactivity
GO:0030097 hemopoiesis
GO:0030183 B cell differentiation
GO:0030595 leukocyte chemotaxis
GO:0030886 negative regulation of myeloid dendritic cell activation
GO:0030889 negative regulation of B cell proliferation
GO:0032496 response to lipopolysaccharide
GO:0032689 negative regulation of interferon-gamma production
GO:0032695 negative regulation of interleukin-12 production
GO:0032715 negative regulation of interleukin-6 production
GO:0032720 negative regulation of tumor necrosis factor production
GO:0032800 receptor biosynthetic process
GO:0032868 response to insulin
GO:0034465 response to carbon monoxide
GO:0042092 type 2 immune response
GO:0042100 B cell proliferation
GO:0042130 negative regulation of T cell proliferation
GO:0042493 response to drug
GO:0042536 negative regulation of tumor necrosis factor biosynthetic process
GO:0042742 defense response to bacterium
GO:0043066 negative regulation of apoptotic process
GO:0044130 negative regulation of growth of symbiont in host
GO:0045019 negative regulation of nitric oxide biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045191 regulation of isotype switching
GO:0045347 negative regulation of MHC class II biosynthetic process
GO:0045348 positive regulation of MHC class II biosynthetic process
GO:0045355 negative regulation of interferon-alpha biosynthetic process
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050715 positive regulation of cytokine secretion
GO:0050728 negative regulation of inflammatory response
GO:0051045 negative regulation of membrane protein ectodomain proteolysis
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051384 response to glucocorticoid
GO:0051930 regulation of sensory perception of pain
GO:0060670 branching involved in labyrinthine layer morphogenesis
GO:0071222 cellular response to lipopolysaccharide
GO:0071392 cellular response to estradiol stimulus
Cellular Component
GO:0005615 extracellular space
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
KEGG
Cytokine-cytokine receptor interaction pathway
Jak-STAT signaling pathway pathway
T cell receptor signaling pathway pathway
Intestinal immune network for IgA production pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Toxoplasmosis pathway
Amoebiasis pathway
Staphylococcus aureus infection pathway
Asthma pathway
Autoimmune thyroid disease pathway
Systemic lupus erythematosus pathway
Allograft rejection pathway
INOH
GPCR signaling pathway
IL-10 signaling pathway
JAK STAT pathway and regulation pathway
PID BIOCARTA
Il-10 anti-inflammatory signaling pathway [Biocarta view]
PID NCI
AP-1 transcription factor network
IL4-mediated signaling events
Regulation of nuclear SMAD2/3 signaling
Cross-References
SwissProt P22301
TrEMBL Q6FGW4 Q6LBF4 Q71UZ1
UniProt Splice Variant
Entrez Gene 3586
UniGene Hs.193717
RefSeq NM_000572
HUGO HGNC:5962
OMIM 124092
CCDS CCDS1467
HPRD 00495
IMGT
EMBL AF043333 AF418271 AY029171 BC104252 BC104253 CH471100 CR541993 DQ217938 GQ405199 M57627 U16720 X78437
GenPept AAA63207 AAA80104 AAC03534 AAI04253 AAI04254 AAK38162 AAL06594 ABB01008 ACV30066 CAA55201 CAG46790 EAW93524
RNA Seq Atlas 3586