Interleukin 22

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Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.[1][2]


IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits.[3] IL-22R is expressed on tissue cells, and it is absent on immune cells.[4]

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.[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),[5] 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.[6] 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 [7] 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.[8]

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.[3] 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.[9] In some contexts, the pro-inflammatory versus tissue-protective functions of IL-22 are regulated by the often co-expressed cytokine IL-17A [10]

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.[11]


IL-22, signals through the interferon receptor-related proteins CRF2-4 and IL-22R.[2] 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.


  1. 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 27764. PMID 10954742.
  2. 2.0 2.1 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.
  3. 3.0 3.1 3.2 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 2637415. PMID 18599299.
  4. 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.
  5. 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.
  6. 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.
  7. 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 2626689. PMID 19114665.
  8. 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.
  9. 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..
  10. 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 2882840. PMID 20498020.
  11. 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. PMC 4230743. PMID 25408874.

Further reading