interleukin 22

IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. IL-22R is expressed on tissue cells, and it is absent on immune cells.{{cite journal | vauthors = Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R | title = IL-22 increases the innate immunity of tissues | journal = Immunity | volume = 21 | issue = 2 | pages = 241–54 | date = August 2004 | pmid = 15308104 | doi = 10.1016/j.immuni.2004.07.007 | doi-access = free }}

Crystallization 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.

IL-22 is produced by several populations of immune cells at a site of inflammation. Producers are αβ T-cell classes T_h1, T_h22 and T_h17 along with γδ T cells, NKT, ILC3, neutrophils and macrophages. IL-22 takes effect on non-hematopoietic cells – mainly stromal and epithelial cells. Effects involve stimulation of cell survival, proliferation and synthesis of antimicrobials including S100, Reg3β, Reg3γ and defensins. IL-22 thus participates in both wound healing and in protection against microbes.{{cite journal | vauthors = Dudakov JA, Hanash AM, van den Brink MR | title = Interleukin-22: immunobiology and pathology | journal = Annual Review of Immunology | volume = 33 | issue = 1 | pages = 747–85 | date = 2015-03-21 | pmid = 25706098 | doi = 10.1146/annurev-immunol-032414-112123 | pmc = 4407497 }} IL-22 dysregulation takes part in pathogenesis of several autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and psoriasis.{{cite journal | vauthors = Pan HF, Li XP, Zheng SG, Ye DQ | title = Emerging role of interleukin-22 in autoimmune diseases | journal = Cytokine & Growth Factor Reviews | volume = 24 | issue = 1 | pages = 51–7 | date = February 2013 | pmid = 22906768 | doi = 10.1016/j.cytogfr.2012.07.002 | pmc = 4003867 }} 

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.{{PDB|3DGC}}; {{cite journal | vauthors = Jones BC, Logsdon NJ, Walter MR | title = Structure of IL-22 bound to its high-affinity IL-22R1 chain | journal = Structure | volume = 16 | issue = 9 | pages = 1333–44 | date = September 2008 | pmid = 18599299 | pmc = 2637415 | doi = 10.1016/j.str.2008.06.005 }} 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.{{cite journal | vauthors = Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A | title = Interleukin-10 and the interleukin-10 receptor | journal = Annual Review of Immunology | volume = 19 | pages = 683–765 | year = 2001 | pmid = 11244051 | doi = 10.1146/annurev.immunol.19.1.683 }}. In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A {{cite journal | vauthors = Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D | title = Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A | journal = The Journal of Experimental Medicine | volume = 207 | issue = 6 | pages = 1293–305 | date = June 2010 | pmid = 20498020 | pmc = 2882840 | doi = 10.1084/jem.20092054 }}

Targets of this cytokine are mostly non-hematopoietic cells – epithelial and stromal cells of following tissues and organs: liver, lung, skin, thymus, pancreas, kidney, gastrointestinal tract, synovial tissues, heart, breast, eye and adipose tissue.

IL-22 is 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),{{cite journal | vauthors = Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB | title = Interleukin-10 and related cytokines and receptors | journal = Annual Review of Immunology | volume = 22 | pages = 929–79 | year = 2004 | pmid = 15032600 | doi = 10.1146/annurev.immunol.22.012703.104622 }} a class of potent mediators of cellular inflammatory responses. It shares use of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28A/B and IL-29.{{cite journal | vauthors = Witte K, Witte E, Sabat R, Wolk K | title = IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties | journal = Cytokine & Growth Factor Reviews | volume = 21 | issue = 4 | pages = 237–51 | date = August 2010 | pmid = 20655797 | doi = 10.1016/j.cytogfr.2010.04.002 }}

IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.{{cite journal | vauthors = Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL | display-authors = 6 | title = Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R | journal = The Journal of Biological Chemistry | volume = 275 | issue = 40 | pages = 31335–9 | date = October 2000 | pmid = 10875937 | doi = 10.1074/jbc.M005304200 | doi-access = free }} 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.

IL-22 production is induced mainly through IL-23 receptor signalling. IL-23 is produced by dendritic cells after recognition of ligands by specific Toll-like receptors especially in combination with Dectin-1 and or NOD2 signalling. IL-1β stimulates IL-22 production too. On the other hand IL-22 binding protein is a soluble inhibitor which blocks receptor binding site of IL-22.

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{{Interleukins}}

{{Interleukin receptor modulators}}

Category:Interleukins