Mechanisms of Pediatric Inflammatory Bowel Disease

Author:

Peloquin Joanna M.123,Goel Gautam23,Villablanca Eduardo J.123,Xavier Ramnik J.12345

Affiliation:

1. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease and

2. Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114

3. Harvard Medical School, Boston, Massachusetts 02115;, , ,

4. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142

5. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Abstract

Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, is characterized by chronic intestinal inflammation due to a complex interaction of genetic determinants, disruption of mucosal barriers, aberrant inflammatory signals, loss of tolerance, and environmental triggers. Importantly, the incidence of pediatric IBD is rising, particularly in children younger than 10 years. In this review, we discuss the clinical presentation of these patients and highlight environmental exposures that may affect disease risk, particularly among people with a background genetic risk. With regard to both children and adults, we review advancements in understanding the intestinal epithelium, the mucosal immune system, and the resident microbiota, describing how dysfunction at any level can lead to diseases like IBD. We conclude with future directions for applying advances in IBD genetics to better understand pathogenesis and develop therapeutics targeting key pathogenic nodes.

Publisher

Annual Reviews

Subject

Immunology,Immunology and Allergy

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