Lookup NU author(s): Dr Chris Lamb
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.
© 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.
Author(s): Lamb CA, O'Byrne S, Keir ME, Butcher EC
Publication type: Review
Publication status: Published
Journal: Journal of Crohn's and Colitis
Issue: suppl. 2
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