Interleukin 10

Interleukin 10
PDB rendering based on 2H24.
Available structures PDB 1ILK, 1INR, 1J7V, 1LK3, 1Y6K, 2H24, 2ILK
Identifiers
Symbols	IL10; CSIF; IL-10; IL10A; MGC126450; MGC126451; TGIF
External IDs	OMIM: 124092 MGI: 96537 HomoloGene: 478 GeneCards: IL10 Gene
Gene Ontology Molecular function • cytokine activity • interleukin-10 receptor binding • protein binding • growth factor activity Cellular component • extracellular region • extracellular space Biological process • response to molecule of bacterial origin • negative regulation of cytokine secretion involved in immune response • negative regulation of chronic inflammatory response to antigenic stimulus • positive regulation of B cell apoptosis • anti-apoptosis • response to stress • inflammatory response • cytoplasmic sequestering of NF-kappaB • cell-cell signaling • regulation of gene expression • response to activity • hemopoiesis • B cell differentiation • leukocyte chemotaxis • negative regulation of myeloid dendritic cell activation • negative regulation of B cell proliferation • response to lipopolysaccharide • negative regulation of interferon-gamma production • negative regulation of interleukin-12 production • negative regulation of interleukin-6 production • negative regulation of tumor necrosis factor production • receptor biosynthetic process • response to insulin stimulus • response to carbon monoxide • type 2 immune response • B cell proliferation • negative regulation of T cell proliferation • response to drug • negative regulation of tumor necrosis factor biosynthetic process • defense response to bacterium • negative regulation of growth of symbiont in host • negative regulation of nitric oxide biosynthetic process • regulation of isotype switching • negative regulation of MHC class II biosynthetic process • positive regulation of MHC class II biosynthetic process • negative regulation of interferon-alpha biosynthetic process • positive regulation of transcription, DNA-dependent • positive regulation of cytokine secretion • negative regulation of inflammatory response • negative regulation of membrane protein ectodomain proteolysis • positive regulation of sequence-specific DNA binding transcription factor activity • response to glucocorticoid stimulus • regulation of sensory perception of pain • branching involved in embryonic placenta morphogenesis • cellular response to estradiol stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3586	16153
Ensembl	ENSG00000136634	ENSMUSG00000016529
UniProt	P22301	Q0VBJ1
RefSeq (mRNA)	NM_000572.2	NM_010548.2
RefSeq (protein)	NP_000563.1	NP_034678.1
Location (UCSC)	Chr 1: 206.94 – 206.95 Mb	Chr 1: 132.92 – 132.92 Mb
PubMed search	[1]	[2]

Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene.

This cytokine is 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 antigens, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-κB 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. and indeed patients with Crohn's disease react favorably towards treatment with bacteria producing recombinant interleukin 10, showing the importance of interleukin 10 for counteracting excessive immunity in the human body.

A study in mice has shown that interleukin-10 is also produced by mast cells, counteracting the inflammatory effect that these cells have at the site of an allergic reaction.

Function

IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and regulatory T-cells. It also displays a potent ability to suppress the antigen-presentation capacity of antigen presenting cells. However, it is also stimulatory towards certain T cells and mast cells and stimulates B cell maturation and antibody production.

Expression

It is mainly expressed in monocytes and Type 2 T helper cells (T_H2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and also in a certain subset of activated T cells and B cells. Said et al. showed that IL-10 can also be produced by monocytes upon PD-1 triggering in these cells.

It is released by cytotoxic T-cells to inhibit the actions of NK cells during the immune response to viral infection.

Gene and protein structure

In humans, the IL-10 gene is located in chromosome 1 and consists of 5 exons.

The IL-10 protein is a homodimer . Each subunit is 178 amino acids long.

Interleukin 10 is classified as a class 2 cytokine. The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29)

Interactions

Interleukin 10 has been shown to interact with Interleukin 10 receptor, alpha subunit.

The receptor complex for interleukin-10 also requires the IL10R2 chain to initiate signaling. This ligand:receptor combination is found in birds and frogs, and likely also exists in bony fish.

Further reading

• Bortesi L, Rossato M, Schuster F, Raven N, Stadlmann J, Avesani L, Falorni A, Bazzoni F, Bock R, Schillberg S, Pezzotti M (2009). "Viral and murine interleukin-10 are correctly processed and retain their biological activity when produced in tobacco". BMC Biotechnol. 9: 22. doi:10.1186/1472-6750-9-22. PMC 2667500. PMID 19298643. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2667500. 
• Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001). "Interleukin-10 and the interleukin-10 receptor". Annu. Rev. Immunol. 19: 683–765. doi:10.1146/annurev.immunol.19.1.683. PMID 11244051. 
• Girndt M (2003). "Humoral immune responses in uremia and the role of IL-10". Blood Purif. 20 (5): 485–8. doi:10.1159/000063553. PMID 12207099. 
• Beebe AM, Cua DJ, de Waal Malefyt R (2003). "The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS)". Cytokine Growth Factor Rev. 13 (4–5): 403–12. doi:10.1016/S1359-6101(02)00025-4. PMID 12220553. 
• Mocellin S, Panelli MC, Wang E, et al. (2004). "The dual role of IL-10". Trends Immunol. 24 (1): 36–43. doi:10.1016/S1471-4906(02)00009-1. PMID 12495723. 
• Roncarolo MG, Battaglia M, Gregori S (2004). "The role of interleukin 10 in the control of autoimmunity". J. Autoimmun. 20 (4): 269–72. doi:10.1016/S0896-8411(03)00047-7. PMID 12791310. 
• Groux H, Cottrez F (2004). "The complex role of interleukin-10 in autoimmunity". J. Autoimmun. 20 (4): 281–5. doi:10.1016/S0896-8411(03)00044-1. PMID 12791313. 
• Llorente L, Richaud-Patin Y (2004). "The role of interleukin-10 in systemic lupus erythematosus". J. Autoimmun. 20 (4): 287–9. doi:10.1016/S0896-8411(03)00043-X. PMID 12791314. 
• Asadullah K, Sabat R, Friedrich M, et al. (2004). "Interleukin-10: an important immunoregulatory cytokine with major impact on psoriasis". Current drug targets. Inflammation and allergy 3 (2): 185–92. doi:10.2174/1568010043343886. PMID 15180472. 
• Stenvinkel P, Ketteler M, Johnson RJ, et al. (2005). "IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly". Kidney Int. 67 (4): 1216–33. doi:10.1111/j.1523-1755.2005.00200.x. PMID 15780075. 
• Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini reviews in medicinal chemistry 5 (12): 1093–101. doi:10.2174/138955705774933383. PMID 16375755. 

External links

• MeSH Interleukin-10