Inflammatory bowel disease

Abstract

Insights into inflammatory bowel disease (IBD) are advancing rapidly owing to immunologic investigations of a plethora of animal models of intestinal inflammation, ground-breaking advances in the interrogation of diseases that are inherited as complex genetic traits, and the development of culture-independent methods to define the composition of the intestinal microbiota. These advances are bringing a deeper understanding to the genetically determined interplay between the commensal microbiota, intestinal epithelial cells, and the immune system and the manner in which this interplay might be modified by relevant environmental factors in the pathogenesis of IBD. This review examines these interactions and, where possible, potential lessons from IBD-directed, biologic therapies that may allow for elucidation of pathways that are central to disease pathogenesis in humans.

Figures

Figure 1

Inflammatory bowel disease (IBD) as a multifactorial disorder. The development and course of IBD are affected by several factors, including genetic susceptibility of the host, the intestinal microbiota, other environmental factors, and the host immune system. In addition, these factors cross-regulate each other in multiple ways, as shown. IBD-associated genes are summarized by molecular pathways with genes belonging to the same pathway arranged next to each other in one line. Polymorphisms in genes specific for Crohn’s disease (CD) are shown in magenta text, whereas those specific for ulcerative colitis (UC) are shown in dark blue text. Genetic associations shared between both diseases are shown in black text. Abbreviations: HSPs, heat shock proteins; MHC, major histocompatibility complex; NSAIDs, nonsteroidal anti-inflammatory drugs; PRR, pattern-recognition receptor; RA, retinoic acid; ROS, reactive oxygen species; TSLP, thymic stromal lymphopoietin.

Figure 2

The microbial flora, intestinal epithelial cells, and lamina propria immune cells as targets, participants, and central organizers in intestinal immune responses. Abbreviations: EGF, epithelial growth factor; KGF, keratinocyte growth factor; PAMPs, pathogen-associated molecular patterns; PRR, pattern-recognition receptor.