Role of interleukin-22 in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses. Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract, leading to further inflammation. Interleukin (IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells. Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3 signaling cascades. This cytokine induces antimicrobial molecules and proliferative and antiapoptotic pathways, which help prevent tissue damage and aid in its repair. All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity. In this review, we discuss recent progress in the involvement of IL-22 in the pathogenesis of IBD, as well as its therapeutic potential.

The role of barrier function, autophagy, and cytokines in maintaining intestinal homeostasis

“…This cytokine has both proinflammatory and anti-inflammatory functions but studies suggest a protective role for IL-22 in the gut. IL-22 is member of the IL-10 cytokine family, and is produced by innate lymphoid cells, dendritic cells, neutrophils and various subtypes of CD4+ T cells, most notably; Th17, Th1 and Th22 cells [101,102]. IL-22 is recognized by a heterodimeric receptor complex composed of two subunits, IL-10R2 which is expressed on a broad array of tissues and IL-22R1, which is expressed in a limited number of tissues including the intestine, lung and skin [103].…”

Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update)

“…In context of protective role of ILC22, IL-22 actives antimicrobial molecules and antiapoptotic pathways that contribute to inhibition of tissue damage and tissue repair. These activities involve in elevation of intestinal barrier integrity and epithelial innate immunity [120]. In one study, it has been shown in a mouse model that IL-23 in colon can stimulate RORct+ ILCs in order to secrete IL-17 and induce intestinal colitis [119].…”

Profile of interleukin-22 in gut mucosal health and disease

“…126 Moreover, a recent study demonstrated that IFN-γ/IL-17-coproducing CD4+ T-cells specifically enriched in the inflamed mucosal tissue of patients with IBD also showed high expression levels of However, data from mouse models support an important protective role of IL-22 in IBD. 35,129 In humans, a loss of the Th22 subset has been reported in the colon of patients with UC, 130 whereas IL-22 production by ILCs has been seen to be impaired in inflamed tissue of patients with CD; 58 increased production of IL-22BP, a negative regulator of IL-22 function, has also been observed in human IBD. 96 A protective role of IL-22 in human IBD; in this case, UC is further supported by the report of amelioration of symptoms in an individual who deliberately infected themselves with Trichuris trichiura, resulting in an expansion of IL-22-producing CD4+ T-cells.…”

“…131 Thus, it seems that IL-22 can also be beneficial in the context of IBD, which is perhaps not surprising given its capacity to directly interact with gut epithelia and mediate tissue repair in this context. 53 However, the suggestion that IL-22 represents a potential therapeutic candidate for IBD 129 has to be balanced against the evidence supporting a role of this cytokine in IBD pathogenesis. …”