Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22gene.[5][6]
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.[7] IL-22R is expressed on tissue cells, and it is absent on immune cells.[8]
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.[7]
Function
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),[9] 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.[10] 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 [11] and also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive innate immune systems, autoimmunity and tissue regeneration.[12]
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.[7] 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.[13] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [14]
IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.[6] 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.
^ abXie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL (Oct 2000). "Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R". The Journal of Biological Chemistry. 275 (40): 31335–9. doi:10.1074/jbc.M005304200. PMID10875937.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (Aug 2004). "IL-22 increases the innate immunity of tissues". Immunity. 21 (2): 241–54. doi:10.1016/j.immuni.2004.07.007. PMID15308104.
^Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001). "Interleukin-10 and the interleukin-10 receptor". Annual Review of Immunology. 19: 683–765. doi:10.1146/annurev.immunol.19.1.683. PMID11244051..
^Hill T, Krougly O, Nikoopour E, Bellemore S, Lee-Chan E, Fouser LA, Hill DJ, Singh B (2013). "The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes". Cell Regeneration. 2 (1): 2. doi:10.1186/2045-9769-2-2. PMID25408874.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Further reading
Weger W, Hofer A, Wolf P, El-Shabrawi Y, Renner W, Kerl H, Salmhofer W (Sep 2009). "Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis". Experimental Dermatology. 18 (9): 796–8. doi:10.1111/j.1600-0625.2009.00840.x. PMID19469905.
Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, Hibberd ML, Seielstad M (Apr 2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes and Immunity. 11 (3): 232–8. doi:10.1038/gene.2010.1. PMID20237496.
Silverberg MS, Cho JH, Rioux JD, McGovern DP, Wu J, Annese V, Achkar JP, Goyette P, Scott R, Xu W, Barmada MM, Klei L, Daly MJ, Abraham C, Bayless TM, Bossa F, Griffiths AM, Ippoliti AF, Lahaie RG, Latiano A, Paré P, Proctor DD, Regueiro MD, Steinhart AH, Targan SR, Schumm LP, Kistner EO, Lee AT, Gregersen PK, Rotter JI, Brant SR, Taylor KD, Roeder K, Duerr RH (Feb 2009). "Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study". Nature Genetics. 41 (2): 216–20. doi:10.1038/ng.275. PMC2652837. PMID19122664.
de Moura PR, Watanabe L, Bleicher L, Colau D, Dumoutier L, Lemaire MM, Renauld JC, Polikarpov I (Apr 2009). "Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22". FEBS Letters. 583 (7): 1072–7. doi:10.1016/j.febslet.2009.03.006. PMID19285080.
Wong CK, Lun SW, Ko FW, Wong PT, Hu SQ, Chan IH, Hui DS, Lam CW (2009). "Activation of peripheral Th17 lymphocytes in patients with asthma". Immunological Investigations. 38 (7): 652–64. doi:10.1080/08820130903062756. PMID19811428.
Shen H, Goodall JC, Hill Gaston JS (Jun 2009). "Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis". Arthritis and Rheumatism. 60 (6): 1647–56. doi:10.1002/art.24568. PMID19479869.
Thompson CL, Plummer SJ, Tucker TC, Casey G, Li L (Aug 2010). "Interleukin-22 genetic polymorphisms and risk of colon cancer". Cancer Causes & Control. 21 (8): 1165–70. doi:10.1007/s10552-010-9542-5. PMID20339910.
Pan HF, Zhao XF, Yuan H, Zhang WH, Li XP, Wang GH, Wu GC, Tang XW, Li WX, Li LH, Feng JB, Hu CS, Ye DQ (Mar 2009). "Decreased serum IL-22 levels in patients with systemic lupus erythematosus". Clinica Chimica Acta; International Journal of Clinical Chemistry. 401 (1–2): 179–80. doi:10.1016/j.cca.2008.11.009. PMID19046958.
Liu Y, Yang B, Zhou M, Li L, Zhou H, Zhang J, Chen H, Wu C (Jun 2009). "Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans". European Journal of Immunology. 39 (6): 1472–9. doi:10.1002/eji.200838811. PMID19449309.
Sekikawa A, Fukui H, Suzuki K, Karibe T, Fujii S, Ichikawa K, Tomita S, Imura J, Shiratori K, Chiba T, Fujimori T (Mar 2010). "Involvement of the IL-22/REG Ialpha axis in ulcerative colitis". Laboratory Investigation. 90 (3): 496–505. doi:10.1038/labinvest.2009.147. PMID20065946.
He M, Liang P (Feb 2010). "IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis". Journal of Immunology. 184 (4): 1793–8. doi:10.4049/jimmunol.0901829. PMID20061404.
Wolk K, Witte E, Warszawska K, Schulze-Tanzil G, Witte K, Philipp S, Kunz S, Döcke WD, Asadullah K, Volk HD, Sterry W, Sabat R (Dec 2009). "The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis". European Journal of Immunology. 39 (12): 3570–81. doi:10.1002/eji.200939687. PMID19830738.
Dhiman R, Indramohan M, Barnes PF, Nayak RC, Paidipally P, Rao LV, Vankayalapati R (Nov 2009). "IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by enhancing phagolysosomal fusion". Journal of Immunology. 183 (10): 6639–45. doi:10.4049/jimmunol.0902587. PMID19864591.
Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M (Feb 2009). "A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity". Nature. 457 (7230): 722–5. doi:10.1038/nature07537. PMID18978771.
