Front. Immunol., 17 September 2013 | doi: 10.3389/fimmu.2013.00280
- 1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- 2Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
- 3Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
The gut mucosa is constantly challenged by a bombardment of foreign antigens and environmental microorganisms. As such, the precise regulation of the intestinal barrier allows the maintenance of mucosal immune homeostasis and prevents the onset of uncontrolled inflammation. In support of this concept, emerging evidence points to defects in components of the epithelial barrier as etiologic factors in the pathogenesis of inflammatory bowel diseases (IBDs). In fact, the integrity of the intestinal barrier relies on different elements, including robust innate immune responses, epithelial paracellular permeability, epithelial cell integrity, as well as the production of mucus. The purpose of this review is to systematically evaluate how alterations in the aforementioned epithelial components can lead to the disruption of intestinal immune homeostasis, and subsequent inflammation. In this regard, the wealth of data from mouse models of intestinal inflammation and human genetics are pivotal in understanding pathogenic pathways, for example, that are initiated from the specific loss of function of a single protein leading to the onset of intestinal disease. On the other hand, several recently proposed therapeutic approaches to treat human IBD are targeted at enhancing different elements of gut barrier function, further supporting a primary role of the epithelium in the pathogenesis of chronic intestinal inflammation and emphasizing the importance of maintaining a healthy and effective intestinal barrier.
Keywords: intestinal epithelial cells, intestinal barrier function, gut immune homeostasis, innate immunity, Crohn’s disease, ulcerative colitis, inflammatory bowel disease genetics, animal models of intestinal inflammation
Citation: Pastorelli L, De Salvo C, Mercado JR, Vecchi M and Pizarro TT (2013) Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front. Immunol. 4:280. doi: 10.3389/fimmu.2013.00280
Received: 09 May 2013; Paper pending published: 24 July 2013;
Accepted: 29 August 2013; Published online: 17 September 2013.
Accepted: 29 August 2013; Published online: 17 September 2013.
Edited by:
Rajaraman D. Eri, University of Tasmania, Australia
Reviewed by:
Diane Bimczok, University of Alabama at Birmingham, USAMarcello Chieppa, IRCCS de Bellis, Italy
Copyright: © 2013 Pastorelli, De Salvo, Mercado, Vecchi and Pizarro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Theresa T. Pizarro, Department of Pathology, Case Western Reserve University School of Medicine, 2103 Cornell Road, WRB 5534, Cleveland, OH 44106, USA e-mail: theresa.pizarro@case.edu
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