Role of regenerating islet-derived proteins in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide. It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens, inappropriate activation of the immune system and ultimately to the damage of intestinal tissues. Although numerous efforts have been made to improve the disease management, IBD remains persistently recurring and beyond cure. This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment. However, some recent discoveries, including the beneficial effects of interleukin-22 (IL-22) on the inflamed intestine, have shed light on a self-protective mechanism in IBD. Regenerating islet-derived (REG/Reg) proteins are small secretory proteins which function as IL-22's downstream effectors. Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine, but with undefined mechanisms and roles. The reported functions of REG/Reg proteins in intestinal homeostasis, such as those of antibacterial, anti-inflammatory and tissue repair, lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.

Keywords: Crohn’s disease; Inflammatory bowel disease; Interleukin-22; Intestinal bacteria; Regenerating islet-derived proteins; Ulcerative colitis.

Figure 1

A model of the differential transcription of REG genes in colon crypt cells in Crohn’s disease and ulcerative colitis. Increased interleukin-22 induced transcriptions of REG1/3 in Crohn’s disease (orange solid arrows) are relatively attenuated in ulcerative colitis (orange dotted arrows), leading to CDX2-activated REG transcriptions in ulcerative colitis (black solid arrows), but not in Crohn’s disease (black dotted arrows). IL: Interleukin; TGF: Transforming growth factor; TLR: Toll-like receptor.

Figure 2

A mechanistic model of REG proteins’ protective activities in inflammatory bowel disease. IBD: Inflammatory bowel disease.