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Gene Review

IL22  -  interleukin 22

Homo sapiens

Synonyms: Cytokine Zcyto18, IL-10-related T-cell-derived-inducible factor, IL-21, IL-22, IL-D110, ...
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Disease relevance of IL22


High impact information on IL22

  • The effect of IL-21-treated epithelial cell supernatants on blood lymphocyte migration was assessed using a chemotaxis assay [6].
  • Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts [1].
  • CONCLUSIONS: IL-22 derived from activated T cells acts on SEMFs to elicit expression of proinflammatory cytokines and matrix-degrading molecules indicating proinflammatory/remodeling roles in IBD [1].
  • MAP-kinase inhibitors (PD98059, U0216, and SB202190) significantly reduced IL-22 induction of cytokine secretion [1].
  • 2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits [7].

Chemical compound and disease context of IL22


Biological context of IL22


Anatomical context of IL22


Associations of IL22 with chemical compounds

  • Similar acute phase reactant induction was observed in mouse liver upon IL-TIF injection, and IL-TIF expression was found to be rapidly increased after lipopolysaccharide (LPS) injection, suggesting that this cytokine contributes to the inflammatory response in vivo [2].
  • IL-22 messenger RNA and protein expression are significantly elevated in T cell-mediated hepatitis induced by concanavalin A (ConA) but are less extensively elevated in the carbon tetrachloride-induced liver injury model [13].
  • IL-22 also induced serine phosphorylation of STAT3 on Ser(727) [16].
  • IL-22 treatment of EMT6 tumor-bearing mice lead to a decreased tumor size and a reduced tumor cell proliferation in vivo, as determined by 3'-deoxy-3'-fluorothymidine-positron emission tomography scans [17].

Physical interactions of IL22

  • In addition, IL-22 mediates inflammation and binds class II cytokine receptor heterodimers IL-22 RA1/CRF2-4 [3].

Enzymatic interactions of IL22

  • Importantly, IL-22 exposure of EMT6 cells resulted in decreased levels of phosphorylated ERK1/2 and AKT protein kinases, indicating an inhibitory effect of IL-22 on signaling pathways promoting cell proliferation [17].

Regulatory relationships of IL22

  • The high levels of expression of IL-22R1 observed in epithelial cells of the colon and the ability of IL-22 to upregulate production of acute phase proteins and IL-10 in Colo205 cells, suggest a functional role for IL-22 in intestinal inflammation [11].
  • The aim of this study is to identify potential target cells and associated biological activity of IL-22 by identifying cell types that specifically express high levels of IL-22R1 as the expression of IL-10R2 is ubiquitous [11].
  • Further analyses, by real time quantitative PCR, on a panel of chemokines and immune function related genes revealed that IL-22 induced expression of the acute phase proteins alpha-Antichymotrypsin and Serum Amyloid A, as well as IL-10 mRNA and protein production by Colo205 [11].
  • Thus, the soluble receptor designated IL-22BP inhibits IL-22 activity by binding IL-22 and blocking its interaction with the cell surface IL-22R complex [18].
  • In these cells, IL-22 activates biological activities specific for IFN-gamma, such as up-regulation of MHC class I Ag expression [18].

Other interactions of IL22

  • However, in hamster cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional IL-TIF receptor complex [10].
  • Structural differences between these two cytokines, revealed by the crystallographic studies, clearly indicate that, while a homodimer of IL-10 is required for signaling, hIL-22 most probably interacts with its receptor as a monomer [19].
  • These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles [20].
  • Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region [12].
  • Transcripts of IL-19, IL-20, and IL-22 from monocytes were analyzed [21].

Analytical, diagnostic and therapeutic context of IL22


  1. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Andoh, A., Zhang, Z., Inatomi, O., Fujino, S., Deguchi, Y., Araki, Y., Tsujikawa, T., Kitoh, K., Kim-Mitsuyama, S., Takayanagi, A., Shimizu, N., Fujiyama, Y. Gastroenterology (2005) [Pubmed]
  2. Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. Dumoutier, L., Van Roost, E., Colau, D., Renauld, J.C. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. IL-10 subfamily members: IL-19, IL-20, IL-22, IL-24 and IL-26. Conti, P., Kempuraj, D., Frydas, S., Kandere, K., Boucher, W., Letourneau, R., Madhappan, B., Sagimoto, K., Christodoulou, S., Theoharides, T.C. Immunol. Lett. (2003) [Pubmed]
  4. Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2. Li, J., Tomkinson, K.N., Tan, X.Y., Wu, P., Yan, G., Spaulding, V., Deng, B., Annis-Freeman, B., Heveron, K., Zollner, R., De Zutter, G., Wright, J.F., Crawford, T.K., Liu, W., Jacobs, K.A., Wolfman, N.M., Ling, V., Pittman, D.D., Veldman, G.M., Fouser, L.A. Int. Immunopharmacol. (2004) [Pubmed]
  5. Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. Zhang, W., Chen, Y., Wei, H., Zheng, C., Sun, R., Zhang, J., Tian, Z. Clin. Cancer Res. (2008) [Pubmed]
  6. A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Caruso, R., Fina, D., Peluso, I., Stolfi, C., Fantini, M.C., Gioia, V., Caprioli, F., Del Vecchio Blanco, G., Paoluzi, O.A., Macdonald, T.T., Pallone, F., Monteleone, G. Gastroenterology (2007) [Pubmed]
  7. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. Xu, W., Presnell, S.R., Parrish-Novak, J., Kindsvogel, W., Jaspers, S., Chen, Z., Dillon, S.R., Gao, Z., Gilbert, T., Madden, K., Schlutsmeyer, S., Yao, L., Whitmore, T.E., Chandrasekher, Y., Grant, F.J., Maurer, M., Jelinek, L., Storey, H., Brender, T., Hammond, A., Topouzis, S., Clegg, C.H., Foster, D.C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Inhibition of Interleukin-22 Attenuates Bacterial Load and Organ Failure during Acute Polymicrobial Sepsis. Weber, G.F., Schlautkötter, S., Kaiser-Moore, S., Altmayr, F., Holzmann, B., Weighardt, H. Infect. Immun. (2007) [Pubmed]
  9. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Brand, S., Beigel, F., Olszak, T., Zitzmann, K., Eichhorst, S.T., Otte, J.M., Diepolder, H., Marquardt, A., Jagla, W., Popp, A., Leclair, S., Herrmann, K., Seiderer, J., Ochsenkühn, T., Göke, B., Auernhammer, C.J., Dambacher, J. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  10. Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. Kotenko, S.V., Izotova, L.S., Mirochnitchenko, O.V., Esterova, E., Dickensheets, H., Donnelly, R.P., Pestka, S. J. Biol. Chem. (2001) [Pubmed]
  11. Interleukin-22 activates STAT3 and induces IL-10 by colon epithelial cells. Nagalakshmi, M.L., Rascle, A., Zurawski, S., Menon, S., de Waal Malefyt, R. Int. Immunopharmacol. (2004) [Pubmed]
  12. Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region. Koch, O., Rockett, K., Jallow, M., Pinder, M., Sisay-Joof, F., Kwiatkowski, D. Genes Immun. (2005) [Pubmed]
  13. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Radaeva, S., Sun, R., Pan, H.N., Hong, F., Gao, B. Hepatology (2004) [Pubmed]
  14. Cutting edge: immune cells as sources and targets of the IL-10 family members? Wolk, K., Kunz, S., Asadullah, K., Sabat, R. J. Immunol. (2002) [Pubmed]
  15. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. Boniface, K., Bernard, F.X., Garcia, M., Gurney, A.L., Lecron, J.C., Morel, F. J. Immunol. (2005) [Pubmed]
  16. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. Lejeune, D., Dumoutier, L., Constantinescu, S., Kruijer, W., Schuringa, J.J., Renauld, J.C. J. Biol. Chem. (2002) [Pubmed]
  17. IL-22-Mediated Tumor Growth Reduction Correlates with Inhibition of ERK1/2 and AKT Phosphorylation and Induction of Cell Cycle Arrest in the G2-M Phase. Weber, G.F., Gaertner, F.C., Erl, W., Janssen, K.P., Blechert, B., Holzmann, B., Weighardt, H., Essler, M. J. Immunol. (2006) [Pubmed]
  18. Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. Kotenko, S.V., Izotova, L.S., Mirochnitchenko, O.V., Esterova, E., Dickensheets, H., Donnelly, R.P., Pestka, S. J. Immunol. (2001) [Pubmed]
  19. Crystal structure of recombinant human interleukin-22. Nagem, R.A., Colau, D., Dumoutier, L., Renauld, J.C., Ogata, C., Polikarpov, I. Structure (Camb.) (2002) [Pubmed]
  20. Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26. Oral, H.B., Kotenko, S.V., Yilmaz, M., Mani, O., Zumkehr, J., Blaser, K., Akdis, C.A., Akdis, M. Eur. J. Immunol. (2006) [Pubmed]
  21. Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass. Hsing, C.H., Hsieh, M.Y., Chen, W.Y., Cheung So, E., Cheng, B.C., Chang, M.S. Ann. Thorac. Surg. (2006) [Pubmed]
  22. Interleukin-22: a potential immunomodulatory molecule in the lung. Whittington, H.A., Armstrong, L., Uppington, K.M., Millar, A.B. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  23. Crystallization and synchrotron X-ray diffraction studies of human interleukin-22. Nagem, R.A., Lucchesi, K.W., Colau, D., Dumoutier, L., Renauld, J.C., Polikarpov, I. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
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