(immunology) An immunoregulatory cytokine produced by a subset of helper T cells as well as by B lymphocytes and some cells of the uterus during pregnancy, it inhibits secretion (and function) of cytokine by macrophages and the second population of helper T cells called Th1. Abbreviated IL-10.
Interleukin 10
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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.[1]
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.[2] 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.[3]
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.[4]
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Function
It is capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and the Type 1 T helper cells.
IL-10 also displays potent abilities to suppress the antigen presentation capacity of antigen presenting cells.
However, it is also stimulatory towards certain T cells, mast cells and stimulates B cell maturation and antibody production.
Expression
It is mainly expressed in monocytes and Type 2 T helper cells (TH2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and also in a certain subset of activated T cells and B 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.[1]
The IL-10 protein is a homodimer . Each subunit is 178 amino acids long.[5]
Interactions
Interleukin 10 has been shown to interact with Interleukin 10 receptor, alpha subunit.[6][7][8][9][10]
References
- ^ a b Eskdale J, Kube D, Tesch H, Gallagher G (1997). "Mapping of the human IL10 gene and further characterization of the 5' flanking sequence". Immunogenetics 46 (2): 120–8. PMID 9162098.
- ^ "Entrez Gene: IL10 interleukin 10". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3586.
- ^ Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP, Steidler L (June 2006). "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease". Clin. Gastroenterol. Hepatol. 4 (6): 754–9. doi:. PMID 16716759.
- ^ Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (October 2007). "Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B". Nat. Immunol. 8 (10): 1095–104. doi:. PMID 17767162.
- ^ Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (June 1995). "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma". Structure 3 (6): 591–601. PMID 8590020.
- ^ Ho, A S; Liu Y, Khan T A, Hsu D H, Bazan J F, Moore K W (Dec. 1993). "A receptor for interleukin 10 is related to interferon receptors". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 90 (23): 11267-71. ISSN 0027-8424. PMID 8248239.
- ^ Josephson, K; Logsdon N J, Walter M R (Jul. 2001). "Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site". Immunity (United States) 15 (1): 35-46. ISSN 1074-7613. PMID 11485736.
- ^ Tan, J C; Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, Narula S K, Zavodny P J, Chou C C (May. 1995). "Characterization of recombinant extracellular domain of human interleukin-10 receptor". J. Biol. Chem. (UNITED STATES) 270 (21): 12906-11. ISSN 0021-9258. PMID 7759550.
- ^ Josephson, K; McPherson D T, Walter M R (Dec. 2001). "Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1". Acta Crystallogr. D Biol. Crystallogr. (Denmark) 57 (Pt 12): 1908-11. ISSN 0907-4449. PMID 11717514.
- ^ Hoover, D M; Schalk-Hihi C, Chou C C, Menon S, Wlodawer A, Zdanov A (May. 1999). "Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization". Eur. J. Biochem. (GERMANY) 262 (1): 134-41. ISSN 0014-2956. PMID 10231374.
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:. PMID 19298643.
- 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:. PMID 11244051.
- Girndt M (2003). "Humoral immune responses in uremia and the role of IL-10". Blood Purif. 20 (5): 485–8. doi:. 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:. PMID 12220553.
- Mocellin S, Panelli MC, Wang E, et al. (2004). "The dual role of IL-10". Trends Immunol. 24 (1): 36–43. doi:. 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:. PMID 12791310.
- Groux H, Cottrez F (2004). "The complex role of interleukin-10 in autoimmunity". J. Autoimmun. 20 (4): 281–5. doi:. PMID 12791313.
- Llorente L, Richaud-Patin Y (2004). "The role of interleukin-10 in systemic lupus erythematosus". J. Autoimmun. 20 (4): 287–9. doi:. 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:. 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:. PMID 15780075.
- Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini reviews in medicinal chemistry 5 (12): 1093–101. doi:. PMID 16375755.
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