Targeting immune cell circuits and trafficking in inflammatory bowel disease

Abstract

Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are characterized by uncontrolled activation of intestinal immune cells in a genetically susceptible host. Due to the progressive and destructive nature of the inflammatory process in IBD, complications such as fibrosis, stenosis or cancer are frequently observed, which highlights the need for effective anti-inflammatory therapy. Studies have identified altered trafficking of immune cells and pathogenic immune cell circuits as crucial drivers of mucosal inflammation and tissue destruction in IBD. A defective gut barrier and microbial dysbiosis induce such accumulation and local activation of immune cells, which results in a pro-inflammatory cytokine loop that overrides anti-inflammatory signals and causes chronic intestinal inflammation. This Review discusses pathogenic cytokine responses of immune cells as well as immune cell trafficking as a rational basis for new translational therapies in IBD.

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Fig. 1: Clinical features of IBD.
Fig. 2: Pathogenesis of IBD and targets for therapeutic interventions.
Fig. 3: T cell priming and trafficking in IBD.
Fig. 4: Immune cell subsets and cytokines in IBD.

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Acknowledgements

The research of M.F.N. was funded by the DFG (SFB1181, TRR241, FOR2438, SAOT graduate school), by the Interdisciplinary Centre for Clinical Research Erlangen and by the FAU Emerging Fields Initiative.

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Correspondence to Markus F. Neurath.

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M.F.N. has served as an advisor to Pentax, PPD, Abbvie, Boehringer, MSD, Janssen, Roche, Genentech, Shire and Takeda. M.F.N. received research support from Takeda, Boehringer, Roche and Shire.

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Neurath, M.F. Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nat Immunol 20, 970–979 (2019). https://doi.org/10.1038/s41590-019-0415-0

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