Interleukin 22

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IL22 IL22R 3DGC.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesIL22, IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23, TIFa, zcyto18, interleukin 22
External IDsOMIM: 605330 MGI: 2151139 HomoloGene: 9669 GeneCards: IL22
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 12: 68.25 – 68.25 MbChr 10: 118.13 – 118.13 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.[5][6]


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]


IL-22 is produced by several populations of immune cells at a site of inflammation. Producers are αβ T cells classes Th1, Th22 and Th17 along with γδ T cells, NKT, ILC3, neutrophils and macrophages. IL-22 takes effect on non-hematopoietic cells – mainly stromal and epithelial cells. Effects involve stimulation of cell survival, proliferation and synthesis of antimicrobials including S100, Reg3β, Reg3γ and defensins. IL-22 thus participates in both wound healing and in protection against microbes.[9] IL-22 dysregulation takes part in pathogenesis of several autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and psoriasis.[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.[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.[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

Targets of this cytokine are mostly non-hematopoietic cells – epithelial and stromal cells of following tissues and organs: liver, lung, skin, thymus, pancreas, kidney, gastrointestinal tract, synovial tissues, heart, breast, eye and adipose tissue.[9]


IL-22 is 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),[13] 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.[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.

Regulation of production

IL-22 production is induced mainly through IL-23 receptor signalling. IL-23 is produced by dendritic cells after recognition of ligands by specific Toll-like receptors especially in combination with Dectin-1 and or NOD2 signalling. IL-1β stimulates IL-22 production too. On the other hand IL-22 binding protein is a soluble inhibitor which blocks receptor binding site of IL-22.[9]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000127318 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000090461 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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". Proceedings of the National Academy of Sciences of the United States of America. 97 (18): 10144–9. doi:10.1073/pnas.170291697. PMC 27764. PMID 10954742.
  6. ^ a b Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, et al. (October 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.
  7. ^ a b c 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.
  8. ^ Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R (August 2004). "IL-22 increases the innate immunity of tissues". Immunity. 21 (2): 241–54. doi:10.1016/j.immuni.2004.07.007. PMID 15308104.
  9. ^ a b c Dudakov JA, Hanash AM, van den Brink MR (2015-03-21). "Interleukin-22: immunobiology and pathology". Annual Review of Immunology. 33 (1): 747–85. doi:10.1146/annurev-immunol-032414-112123. PMC 4407497. PMID 25706098.
  10. ^ Pan HF, Li XP, Zheng SG, Ye DQ (February 2013). "Emerging role of interleukin-22 in autoimmune diseases". Cytokine & Growth Factor Reviews. 24 (1): 51–7. doi:10.1016/j.cytogfr.2012.07.002. PMC 4003867. PMID 22906768.
  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 (June 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 2882840. PMID 20498020.
  13. ^ 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.
  14. ^ Witte K, Witte E, Sabat R, Wolk K (August 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.

Further reading