Interleukin 22
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 use of IL-10R2 in cell signaling with other members of this family, IL-10, IL-26, IL-28A/B and IL-29[5]. 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 [6] 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.[7] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [8]
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[edit] 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.
[edit] 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]
[edit] 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:10.1016/j.str.2008.06.005. PMC 2637415. PMID 18599299. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2637415.
- ^ 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:10.1073/pnas.170291697. PMC 27764. PMID 10954742. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27764.
- ^ 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:10.1074/jbc.M005304200. 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:10.1146/annurev.immunol.22.012703.104622. PMID 15032600.
- ^ Witte K, Witte E, Sabat R, Wolk K (Aug 2010). "IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties". Cytokine Growth Factor Rev 21 (4): 237–51. doi:10.1016/j.cytogfr.2010.04.002. PMID 20655797.
- ^ 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:10.1084/jem.20072713. PMC 2626689. PMID 19114665. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2626689.
- ^ 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:10.1146/annurev.immunol.19.1.683. PMID 11244051.
- ^ Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D (2010). "Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A". J Exp Med. 207 (6): 1293–305. doi:10.1084/jem.20092054. PMC 2882840. PMID 20498020. http://jem.rupress.org/content/207/6/1293.abstract.
[edit] Further reading
- Weger W, Hofer A, Wolf P, et al. (2009). "Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis". Exp. Dermatol. 18 (9): 796–8. doi:10.1111/j.1600-0625.2009.00840.x. PMID 19469905.
- Davila S, Froeling FE, Tan A, et al. (2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes Immun. 11 (3): 232–8. doi:10.1038/gene.2010.1. PMID 20237496.
- Silverberg MS, Cho JH, Rioux JD, et al. (2009). "Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study". Nat. Genet. 41 (2): 216–20. doi:10.1038/ng.275. PMC 2652837. PMID 19122664. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2652837.
- de Moura PR, Watanabe L, Bleicher L, et al. (2009). "Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22". FEBS Lett. 583 (7): 1072–7. doi:10.1016/j.febslet.2009.03.006. PMID 19285080.
- Wong CK, Lun SW, Ko FW, et al. (2009). "Activation of peripheral Th17 lymphocytes in patients with asthma". Immunol. Invest. 38 (7): 652–64. doi:10.1080/08820130903062756. PMID 19811428.
- Shen H, Goodall JC, Hill Gaston JS (2009). "Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis". Arthritis Rheum. 60 (6): 1647–56. doi:10.1002/art.24568. PMID 19479869.
- Thompson CL, Plummer SJ, Tucker TC, et al. (2010). "Interleukin-22 genetic polymorphisms and risk of colon cancer". Cancer causes & control : CCC 21 (8): 1165–70. doi:10.1007/s10552-010-9542-5. PMID 20339910.
- Hughes T, Becknell B, McClory S, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2673127.
- Siezen CL, Bont L, Hodemaekers HM, et al. (2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes". Pediatr. Infect. Dis. J. 28 (4): 333–5. doi:10.1097/INF.0b013e31818e2aa9. PMID 19258923.
- Pitta MG, Romano A, Cabantous S, et al. (2009). "IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani". J. Clin. Invest. 119 (8): 2379–87. doi:10.1172/JCI38813. PMC 2719936. PMID 19620772. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2719936.
- Pan HF, Zhao XF, Yuan H, et al. (2009). "Decreased serum IL-22 levels in patients with systemic lupus erythematosus". Clin. Chim. Acta 401 (1–2): 179–80. doi:10.1016/j.cca.2008.11.009. PMID 19046958.
- Liu Y, Yang B, Zhou M, et al. (2009). "Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans". Eur. J. Immunol. 39 (6): 1472–9. doi:10.1002/eji.200838811. PMID 19449309.
- Sekikawa A, Fukui H, Suzuki K, et al. (2010). "Involvement of the IL-22/REG Ialpha axis in ulcerative colitis". Lab. Invest. 90 (3): 496–505. doi:10.1038/labinvest.2009.147. PMID 20065946.
- He M, Liang P (2010). "IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis". J. Immunol. 184 (4): 1793–8. doi:10.4049/jimmunol.0901829. PMID 20061404.
- Wolk K, Witte E, Warszawska K, et al. (2009). "The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis". Eur. J. Immunol. 39 (12): 3570–81. doi:10.1002/eji.200939687. PMID 19830738.
- Eyerich S, Eyerich K, Pennino D, et al. (2009). "Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling". J. Clin. Invest. 119 (12): 3573–85. doi:10.1172/JCI40202. PMC 2786807. PMID 19920355. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2786807.
- Dhiman R, Indramohan M, Barnes PF, et al. (2009). "IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by enhancing phagolysosomal fusion". J. Immunol. 183 (10): 6639–45. doi:10.4049/jimmunol.0902587. PMID 19864591.
- Cella M, Fuchs A, Vermi W, et al. (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. PMID 18978771.
- Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA (2009). "Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity". Curr Opin Pharmacol 9 (4): 447–53. doi:10.1016/j.coph.2009.04.008. PMC 2755239. PMID 19481975. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2755239.
- Kagami S, Rizzo HL, Lee JJ, et al. (2010). "Circulating Th17, Th22, and Th1 cells are increased in psoriasis". J. Invest. Dermatol. 130 (5): 1373–83. doi:10.1038/jid.2009.399. PMC 2892169. PMID 20032993. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2892169.
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