Clinical importance of IL-22 cascade in IBD

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.

Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

“…For example, AhR ligands are crucial for activating AhR‐expressing type 3 innate lymphoid cells in the mucosa to produce IL‐22 . IL‐22 promotes mucosal healing by stimulating mucus production and goblet cell reconstitution under inflammatory conditions . Furthermore, AhR signaling has also been reported to induce immune tolerance with the production of IL‐10 .…”

“…23,24 IL-22 promotes mucosal healing 25 by stimulating mucus production and goblet cell reconstitution under inflammatory conditions. [25][26][27] Furthermore, AhR signaling has also been reported to induce immune tolerance with the production of IL-10. 27,28 While these mechanisms have not been confirmed in patients with UC, it seems plausible that AhR plays an important role in its pathophysiology considering the fact that AHR has been identified as a susceptibility locus in UC in genome-wide association studies.…”

Intestinal Stem Cell Aging: Origins and Interventions

“…The role of ISC deregulation in intestinal inflammation and inflammatory disorders is complex, but it is likely that interventions that target ISC function can serve to improve the trajectory of inflammatory bowel diseases. One example is the use of interleukin (IL)-22 as a possible therapy for inflammatory bowel diseases (165,166).…”

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

“…129 Homozygous deletion of IL-17A reduced enthesitis severity, while neutralization of IL-22 reduced enthesitis but exacerbated ileitis, 147 perhaps due to the well-accepted ability of IL-22 to reenforce mucosal barrier integrity. 190,191 It is remarkable that this SKG model and TNF transgenic models exhibit both experimental terminal ileitis and enthesitis in the same model systems in two different strains with two major cytokines that are therapeutic targets in SpA-and enthesitis-related disease.…”