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Intestinal homeostasis and its breakdown in inflammatory bowel disease

Abstract

Intestinal homeostasis depends on complex interactions between the microbiota, the intestinal epithelium and the host immune system. Diverse regulatory mechanisms cooperate to maintain intestinal homeostasis, and a breakdown in these pathways may precipitate the chronic inflammatory pathology found in inflammatory bowel disease. It is now evident that immune effector modules that drive intestinal inflammation are conserved across innate and adaptive leukocytes and can be controlled by host regulatory cells. Recent evidence suggests that several factors may tip the balance between homeostasis and intestinal inflammation, presenting future challenges for the development of new therapies for inflammatory bowel disease.

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Figure 1: Bacterial sensing and cellular stress pathways in intestinal homeostasis.
Figure 2: Conserved innate and adaptive immune effector modules in the gut.
Figure 3: A multihit model of IBD pathogenesis.

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Acknowledgements

We thank M. Asquith, H. Uhlig, P. Ahern and M. Barnes for review and G. Song-Zhao and O. Harrison for help with the figures. We apologize to those whose work was not cited owing to space constraints. K.J.M. and F.P. are supported by grants from the Wellcome Trust, Cancer Research UK and the European Union (FP7, INFLAMMACARE).

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Maloy, K., Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011). https://doi.org/10.1038/nature10208

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