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. 2020 Jun 14;16(13):2323–2339. doi: 10.7150/ijbs.46651

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This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

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IL-22 signaling is transduced through heterodimer receptor complexes composed of IL-10R2 and IL-22. In addition, there is an endogenous antagonist, IL-22BP. The primary downstream signaling targets of IL-22 are STAT3, STAT1 and STAT5, which are activated by the phosphorylation of Jak1 and Tyk2. The role of IL-22 in the process of tumorigenesis is attributed to DNA damage induction through its synergistic interaction with IFN-γ or Hh infection to produce nitrogen oxide intermediates (iNOS). Furthermore, STAT3 can bind to the DMBT1 promoter region, thereby promoting tumour progression. In addition, IL-22 mediates tumour stemness, which is associated with methylation of H3K79 at three core cancer stemness genes, NANOG, SOX2 and Pou5F1.