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World J Gastroenterol. Jan 7, 2014; 20(1): 6-21
Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.6
Immunopathology of inflammatory bowel disease
Kori L Wallace, Li-Bo Zheng, Yoshitake Kanazawa, David Q Shih
Kori L Wallace, Yoshitake Kanazawa, David Q Shih, F Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles CA 90048, United States
Li-Bo Zheng, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Wallace KL drafted and revised the article; Zheng LB and Kanazawa Y revised the article for intellectual content; Shih DQ revised the article for intellectual content and gave final approval of version to be published.
Supported by NIH KO8 DK093578; CCFA Career Development Award 3467 (DQS); F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
Correspondence to: David Q Shih, MD, PhD, F Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 4066, Los Angeles CA 90048, United States. david.shih@csmc.edu
Telephone: +1-310-4237722 Fax: +1-310-4230224
Received: September 9, 2013
Revised: November 7, 2013
Accepted: November 28, 2013
Published online: January 7, 2014
Processing time: 123 Days and 22.4 Hours
Abstract

Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.

Keywords: Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Microbiome; Autophagy; T helper 17; Innate immune system; Adaptive immune system; Innate lymphoid cells; TL1A

Core tip: Inflammatory bowel disease (IBD) results from the complex interactions between susceptibility genes, the environment, the immune system, and the host’s microbiome. It is thought that either a mucosal susceptibility or a defect in sampling of gut luminal antigen leads to activation of the innate immune system that then recruits cells of the adaptive immune system leading to inflammation. This review will detail the interaction of these components in the immunopathogenesis of IBD.