Interleukin 22

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Interleukin 22
IL22 IL22R 3DGC.png
Crystallographic structure of IL-22 (rainbow colored, N-terminus = blue, C-terminus = red) complexed with the IL-22R1 (magenta).[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IL22 ; IL-21; IL-22; IL-D110; IL-TIF; ILTIF; TIFIL-23; TIFa; zcyto18
External IDs OMIM605330 MGI2151139 HomoloGene9669 GeneCards: IL22 Gene
Orthologs
Species Human Mouse
Entrez 50616 50929
Ensembl ENSG00000127318 ENSMUSG00000074695
UniProt Q9GZX6 Q9JJY9
RefSeq (mRNA) NM_020525 NM_016971
RefSeq (protein) NP_065386 NP_058667
Location (UCSC) Chr 12:
68.64 – 68.65 Mb
Chr 10:
118.2 – 118.21 Mb
PubMed search [1] [2]


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]

Signaling[edit]

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.

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.[1] IL-22R is expressed on tissue cells, and it is absent on immune cells.[9]

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.[1]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ Wolk, K; Kunz S; Witte E; Friedrich M; Asadullah K; Sabat R. (2004). "IL-22 increases the innate immunity of tissues". Immunity 21 (2): 241–54. 

Further reading[edit]