Mucosal healing and inflammatory bowel disease: Therapeutic implications and new targets

Abstract

Mucosal healing (MH) is vital in maintaining homeostasis within the gut and protecting against injury and infections. Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair. However, when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results, particularly inflammatory bowel disease (IBD). Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions, with the mechanisms of regulation just beginning to be understood. Consequently, there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes, so tissue damage in the gastrointestinal tract of patients, even those in clinical remission, persists. With increased understanding of the molecular mechanisms of IBD and MH, tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body's own healing response. In this review, we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.

Keywords: Colitis; Inflammation; Injury/repair; Mucosal barrier; Mucosal healing; Therapeutics.

Figure 1

Pictorial depiction of inter-connection between the immune system, inflammation, and microbiota in mucosal inflammation, associated injury, and healing. Left: normal mucosal homeostasis; Middle: Inflammatory lesions damage the mucosal barrier between the gut lumen and the rest of the body. Barrier damage leads to immune cell activation, cytokine release, and feedback cycles of deteriorating inflammation driven by microbes crossing the damaged barrier; Right: Migration of circulating restitutive immune cells to the wound area, the release of repairing cytokines; crosstalk among extracellular matrix and epithelial cells for proliferation and migration; switching of microbiota and cytokines for mucosal healing and functional crypt regeneration.