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.

Keywords: Inflammatory bowel disease; Interleukin-22; Signal transducer and activator of transcription 3.

Figure 1

Interleukin-22 signaling pathway. IL-22 binds to a heterodimeric receptor composed of IL-10R2 and IL-22R1, activating JAK1 and TYK2, which self-phosphorylate, resulting in binding and phosphorylation of STAT3. Then, STAT3 translocates to the nucleus and induces target genes. IL: Interleukin; JAK: Janus kinase; TYK: Tyrosine protein kinase; STAT: Signal transducer and activator of transcription.

Figure 2

Protective function of interleukin-22 in inflammatory bowel disease. In the intestine, innate and adaptive immune cells, cytokines and many of the transcriptional factors can induce and regulate expression of IL-22. Through activation of STAT3 signaling cascades, IL-22 induces antimicrobial molecules and proliferative and antiapoptotic pathways, and helps regenerate goblet cells and produce mucin proteins, which could prevent tissue damage and aid in its repair. IL: Interleukin; STAT: Signal transducer and activator of transcription.