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Gut-selective integrin-targeted therapies for inflammatory bowel disease

Lookup NU author(s): Dr Chris Lamb

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This is the authors' accepted manuscript of a review that has been published in its final definitive form by Oxford University Press, 2018.

For re-use rights please refer to the publisher's terms and conditions.


Abstract

© 2018 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. Integrins are cell surface receptors with bidirectional signalling capabilities that can bind to adhesion molecules in order to mediate homing of leukocytes to peripheral tissues. Gut-selective leukocyte homing is facilitated by interactions between α4β7 and its ligand, mucosal addressin cellular adhesion molecule-1 [MAdCAM-1], while retention of lymphocytes in mucosal tissues is mediated by αEβ7 binding to its ligand E-cadherin. Therapies targeting gut-selective trafficking have shown efficacy in inflammatory bowel disease [IBD], confirming the importance of leukocyte trafficking in disease pathobiology. This review will provide an overview of integrin structure, function and signalling, and highlight the role that these molecules play in leukocyte homing and retention. Anti-integrin therapeutics, including gut-selective antibodies against the β7 integrin subunit [etrolizumab] and the α4β7 integrin heterodimer [vedolizumab and abrilumab], and the non-gut selective anti-α4 integrin [natalizumab], will be discussed, as well as novel targeting approaches using small molecules.


Publication metadata

Author(s): Lamb CA, O'Byrne S, Keir ME, Butcher EC

Publication type: Review

Publication status: Published

Journal: Journal of Crohn's and Colitis

Year: 2018

Volume: 12

Issue: suppl. 2

Pages: S653-S668

Print publication date: 22/08/2018

Online publication date: 15/05/2018

Acceptance date: 02/04/2018

ISSN (print): 1873-9946

ISSN (electronic): 1876-4479

Publisher: Oxford University Press

URL: https://doi.org/10.1093/ecco-jcc/jjy060

DOI: 10.1093/ecco-jcc/jjy060


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