Xiaoyan Sun1, Laura Chalmers2, Xiaobing Fu3, Min Zhao2. 1. Department of Dermatology, University of California Davis School of Medicine , Sacramento, California. ; Department of Ophthalmology, University of California Davis School of Medicine , Sacramento, California. ; Institute for Regenerative Cures, University of California Davis School of Medicine , Sacramento, California. ; Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital , Beijing, People's Republic of China . 2. Department of Dermatology, University of California Davis School of Medicine , Sacramento, California. ; Department of Ophthalmology, University of California Davis School of Medicine , Sacramento, California. ; Institute for Regenerative Cures, University of California Davis School of Medicine , Sacramento, California. 3. Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Trauma Center of Postgraduate Medical School, Chinese PLA General Hospital , Beijing, People's Republic of China .
Abstract
BACKGROUND: Interleukin 22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) are two important regulators of inflammation. Crohn's disease and ulcerative colitis are considered inflammatory bowel diseases (IBDs), due to the belief that these diseases result from dysregulated responses of the intestinal immune system to bacteria present in the commensal flora. THE PROBLEM: It is debated whether a breakdown of immune tolerance is the primary cause of these diseases or occurs downstream of an initial defect of the intestinal barrier and intestinal epithelial cells (IECs). BASIC/CLINICAL SCIENCE ADVANCES: Recent reports suggest a crucial role for IL-22 in the regulation of gut inflammation as well as epithelial barrier integrity. Local IL-22 gene delivery enhances expression of its downstream effector, STAT3, within colonic epithelial cells and induces both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. IEC-specific deletion of STAT3 results in significant susceptibility to experimental colitis with a striking defect in epithelial restitution. STAT3 activation, thus, may regulate immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing. CLINICAL CARE RELEVANCE: The importance of IL-22/STAT3 signaling in IEC wound healing suggests a critical role for epithelial homeostasis in IBDs. CONCLUSION: Effective healing of the IECs could be considered a primary target in the development of treatments for IBDs. IL-22/STAT3 signaling exerts a protective role in the process of intestinal mucosal wound healing and may thereby provide a promising therapeutic approach to the treatment of IBDs.
BACKGROUND:Interleukin 22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) are two important regulators of inflammation. Crohn's disease and ulcerative colitis are considered inflammatory bowel diseases (IBDs), due to the belief that these diseases result from dysregulated responses of the intestinal immune system to bacteria present in the commensal flora. THE PROBLEM: It is debated whether a breakdown of immune tolerance is the primary cause of these diseases or occurs downstream of an initial defect of the intestinal barrier and intestinal epithelial cells (IECs). BASIC/CLINICAL SCIENCE ADVANCES: Recent reports suggest a crucial role for IL-22 in the regulation of gut inflammation as well as epithelial barrier integrity. Local IL-22 gene delivery enhances expression of its downstream effector, STAT3, within colonic epithelial cells and induces both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. IEC-specific deletion of STAT3 results in significant susceptibility to experimental colitis with a striking defect in epithelial restitution. STAT3 activation, thus, may regulate immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing. CLINICAL CARE RELEVANCE: The importance of IL-22/STAT3 signaling in IEC wound healing suggests a critical role for epithelial homeostasis in IBDs. CONCLUSION: Effective healing of the IECs could be considered a primary target in the development of treatments for IBDs. IL-22/STAT3 signaling exerts a protective role in the process of intestinal mucosal wound healing and may thereby provide a promising therapeutic approach to the treatment of IBDs.
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