Interleukin 22

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Species	Human	Mouse
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Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.

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. IL-22R is expressed on tissue cells, and it is absent on immune cells.

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.

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), 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. IL-22 is produced by activated NK 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 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.

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. 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. In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A

Target tissue

Targets of this cytokine are mostly non-hematopoietic cells such as hepatocytes, keratinocytes, and lung and intestinal epithelial cells. Pancreatic islets also express high levels of IL-22 receptor. It has been shown to induce islet beta cell regeneration.

Signaling

IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R. 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.

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. PMID 19469905.
• 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. PMID 20237496.
• 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. PMC 2652837. PMID 19122664.
• 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. PMID 19285080.
• 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. PMID 19811428.
• 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. PMID 19479869.
• 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. PMID 20339910.
• Hughes T, Becknell B, McClory S, Briercheck E, Freud AG, Zhang X, Mao H, Nuovo G, Yu J, Caligiuri MA (Apr 2009). "Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22". Blood. 113 (17): 4008–10. doi:10.1182/blood-2008-12-192443. PMC 2673127. PMID 19244159.
• Siezen CL, Bont L, Hodemaekers HM, Ermers MJ, Doornbos G, Van't Slot R, Wijmenga C, Houwelingen HC, Kimpen JL, Kimman TG, Hoebee B, Janssen R (Apr 2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes". The Pediatric Infectious Disease Journal. 28 (4): 333–5. doi:10.1097/INF.0b013e31818e2aa9. PMID 19258923.
• Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, Argiro L, el Kheir M, Bucheton B, Mary C, El-Safi SH, Dessein A (Aug 2009). "IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani". The Journal of Clinical Investigation. 119 (8): 2379–87. doi:10.1172/JCI38813. PMC 2719936. PMID 19620772.
• 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. PMID 19046958.
• 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. PMID 19449309.
• 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. PMID 20065946.
• 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. PMID 20061404.
• 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. PMID 19830738.
• Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, Cianfarani F, Odorisio T, Traidl-Hoffmann C, Behrendt H, Durham SR, Schmidt-Weber CB, Cavani A (Dec 2009). "Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling". The Journal of Clinical Investigation. 119 (12): 3573–85. doi:10.1172/JCI40202. PMC 2786807. PMID 19920355.
• 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. PMID 19864591.
• 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. PMC 3772687. PMID 18978771.
• Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA (Aug 2009). "Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity". Current Opinion in Pharmacology. 9 (4): 447–53. doi:10.1016/j.coph.2009.04.008. PMC 2755239. PMID 19481975.
• Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A (May 2010). "Circulating Th17, Th22, and Th1 cells are increased in psoriasis". The Journal of Investigative Dermatology. 130 (5): 1373–83. doi:10.1038/jid.2009.399. PMC 2892169. PMID 20032993.