[Frontiers in Bioscience E4, 1451-1477, January 1, 2012]

Current concepts on the immunopathogenesis of inflammatory bowel disease

Puja Vora1,2 David Quan Shih1 Dermot Patrick McGovern1 Stephan Raoul Targan1

1Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Davis Building Room 4066, Los Angeles, CA 90048, USA, 2Department of Medicine, Division of Digestive Diseases, University of California, 200 Medical Plaza Suite 365A, Los Angeles, CA 90095, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Genetics
4. Microbiome
4.1. Characterization of the microbiota
4.2. Host-microbial interactions
5. Alterations in barrier function
5.1. Mucus layer
5.2. Alterations in the epithelial cell barrier
6. Alterations in innate immunity
6.1. Pattern recognition receptors
6.2. Paneth cells
6.3. Autophagy
7. Innate and adaptive interface
8. Alterations in adaptive immunity
8.1. Th17 cells and the IL-23/IL-17 axis
8.2. IL-12
9. Molecular pathway integration
9.1. Gene-gene interactions
9.1.1. TLR8 and TL1A
9.1.2. NOD2 and ATG16L1
9.2. Environmental-gene interactions
10. Perspective
11. Acknowledgements
12. References

1. ABSTRACT

Inflammatory bowel disease (IBD) is comprised of both ulcerative colitis (UC) and Crohn's disease (CD) and is a chronic inflammatory disorder that results from a dysregulated immune response in genetically susceptible individuals. Data from genome-wide association studies (GWAS) have identified approximately 70 genetic loci that confer susceptibility to CD and over 30 loci that are associated with UC. These genetic loci guide the understanding of the molecular mechanisms of these gene products and reveal that alterations in the immune response underlie the pathophysiology of IBD. This review highlights critical areas in the microbiome, innate immune response, and the adaptive immune response that lead to the chronic mucosal inflammation typically seen in IBD.