Interleukin 22

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IL22
IL22 IL22R 3DGC.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IL22, IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23, TIFa, zcyto18, interleukin 22
External IDs OMIM: 605330 MGI: 2151139 HomoloGene: 9669 GeneCards: 50616
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_020525

NM_054079

RefSeq (protein)

NP_065386.1

NP_473420.2

Location (UCSC) Chr 12: 68.25 – 68.25 Mb Chr 10: 118.29 – 118.3 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.[3][4]

Structure[edit]

IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits.[5] IL-22R is expressed on tissue cells, and it is absent on immune cells.[6]

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.[5]

Function[edit]

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),[7] 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.[8] 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 [9] 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.[10]

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.[5] 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.[11] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [12]

Target tissue[edit]

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.[13]

Signaling[edit]

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

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Dumoutier L, Van Roost E, Colau D, Renauld JC (Aug 2000). "Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor". Proceedings of the National Academy of Sciences of the United States of America. 97 (18): 10144–9. doi:10.1073/pnas.170291697. PMC 27764free to read. PMID 10954742. 
  4. ^ a b Xie 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. PMID 10875937. 
  5. ^ a b c PDB: 3DGC​; Jones BC, Logsdon NJ, Walter MR (Sep 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 2637415free to read. PMID 18599299. 
  6. ^ 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. PMID 15308104. 
  7. ^ Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004). "Interleukin-10 and related cytokines and receptors". Annual Review of Immunology. 22: 929–79. doi:10.1146/annurev.immunol.22.012703.104622. PMID 15032600. 
  8. ^ 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 Reviews. 21 (4): 237–51. doi:10.1016/j.cytogfr.2010.04.002. PMID 20655797. 
  9. ^ Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ (Jan 2009). "Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22". The Journal of Experimental Medicine. 206 (1): 35–41. doi:10.1084/jem.20072713. PMC 2626689free to read. PMID 19114665. 
  10. ^ Nikoopour E, Bellemore SM, Singh B (Jul 2015). "IL-22, cell regeneration and autoimmunity". Cytokine. 74 (1): 35–42. doi:10.1016/j.cyto.2014.09.007. PMID 25467639. 
  11. ^ 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. PMID 11244051. .
  12. ^ Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D (Jun 2010). "Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A". The Journal of Experimental Medicine. 207 (6): 1293–305. doi:10.1084/jem.20092054. PMC 2882840free to read. PMID 20498020. 
  13. ^ 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. PMID 25408874. 

Further reading[edit]