Unravelling the pathogenesis of inflammatory bowel disease


Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.

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Figure 1: Histologic hallmarks of IBD: clues to immunopathogenesis.
Figure 2: Patterns of IBD etiopathogenesis.
Figure 3: Several IBD susceptibility gene products modulate host-cell functional response to microbial flora.
Figure 4: Mucosal immune responses to luminal flora are multi-dimensional.


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This work is supported by grants from the NIH (to R.J.X. and D.K.P.).

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Xavier, R., Podolsky, D. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007). https://doi.org/10.1038/nature06005

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