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Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.[2][3]
IL-22 a member of a group of cytokines called the IL-10 family or IL-10 superfamily (including IL-19, IL-20, IL-24, and IL-26),[4] a class of potent mediators of cellular inflammatory responses. It shares us of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28, (?and IL-29?). IL-22 is produced by activated DC and T cells and initiates innate immune responses against bacterial pathogens especially in epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 is rapidly produced by splenic LTi-like cells [5] and can be also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive and innate immune systems.
IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22 and IL-10 receptor chains play a role in cellular targeting and signal transduction to selectively initiate and regulate immune responses.[1] IL-22 can contribute to immune disease through the stimulation of inflammatory responses, S100s and defensins. IL-22 also promotes hepatocyte survival in the liver and epithelial cells in the lung and gut similar to IL-10.[6]
Signaling
IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.[3] It forms cell surface complexes with IL-22R1 and IL-10R2 chains resulting in signal transduction through receptor, IL-10R2. The IL-22/IL-22R1/IL-10R2 complex activates intracellular kinases (JAK1, Tyk2, and MAP kinases) and transcription factors, especially STAT3. It can induce IL-20 and IL-24 signaling when IL-22R1 pairs with IL-20R2.
Structure
IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits.[1]
Crystalization is possible if the N-linked glycosylation sites are removed in mutants of IL-22 bound with high-affinity cell-surface receptor sIL-22R1. The crystallographic asymmetric unit contained two IL-22-sIL-22R1 complexes.[1]
References
- ^ a b c d PDB 3DGC; Jones BC, Logsdon NJ, Walter MR (September 2008). "Structure of IL-22 bound to its high-affinity IL-22R1 chain". Structure 16 (9): 1333–44. doi:. PMID 18599299.
- ^ Dumoutier L, Van Roost E, Colau D, Renauld JC (August 2000). "Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor". Proc. Natl. Acad. Sci. U.S.A. 97 (18): 10144–9. doi:. PMID 10954742.
- ^ a b Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL (October 2000). "Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R". J. Biol. Chem. 275 (40): 31335–9. doi:. PMID 10875937.
- ^ Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004). "Interleukin-10 and related cytokines and receptors". Annu. Rev. Immunol. 22: 929–79. doi:. PMID 15032600.
- ^ Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ. (2009). "Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22.". J Exp Med. 206 (1): 35-41. doi:. PMID 19114665. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626689/?tool=pubmed.
- ^ 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.
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