TY - JOUR
T1 - Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation
T2 - Lessons learned from animal models and human genetics
AU - Pastorelli, Luca
AU - Salvo, Carlo De
AU - Mercado, Joseph R.
AU - Vecchi, Maurizio
AU - Pizarro, Theresa T.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Animal models of intestinal inflammation
KW - Crohn's disease
KW - Gut immune homeostasis
KW - Inflammatory bowel disease genetics
KW - Innate immunity
KW - Intestinal barrier function
KW - Intestinal epithelial cells
KW - Ulcerative colitis
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UR - http://www.scopus.com/inward/citedby.url?scp=84886014303&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2013.00280
DO - 10.3389/fimmu.2013.00280
M3 - Article
AN - SCOPUS:84886014303
VL - 4
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - SEP
M1 - Article 280
ER -