Clinical importance of IL-22 cascade in IBD

J Gastroenterol. 2018 Apr;53(4):465-474. doi: 10.1007/s00535-017-1401-7. Epub 2017 Oct 26.

Abstract

IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimulating the expression of anti-bacterial peptide and mucins. Of note, IL-22 is characterized as a two-faced cytokine that can play not only protective but also deleterious roles in the intestinal inflammation depending on the cytokine environment such as the expression levels of IL-23, T-bet, and IL-22 binding protein. Most importantly, clinical relevance of IL-22 to inflammatory bowel disease has been well highlighted. Mucosal healing, which represents the current therapeutic goal for IBD, can be induced by IL-22. Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis. Despite the beneficial effect of IL-22, continuous activation of the IL-22 pathway increases the risk of colitis-associated cancer, particularly in patients with an extended history of IBD. This review article discusses how IL-22 regulates colitis, how beneficial versus deleterious effects of IL-22 is determined, and why IL-22 represents a promising target for IBD therapy.

Keywords: Ahr; IL-22BP; IL-23; Indigo naturalis; Mucus.

Publication types

  • Review

MeSH terms

  • Gastrointestinal Agents / therapeutic use
  • Genetic Predisposition to Disease
  • Humans
  • Immunity, Mucosal
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Interleukins / immunology*
  • Intestine, Large / immunology
  • Intestine, Small / immunology
  • Molecular Targeted Therapy / methods
  • Mucus / immunology
  • STAT3 Transcription Factor / metabolism
  • Wound Healing / immunology

Substances

  • Gastrointestinal Agents
  • Interleukins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • interleukin-22