Gut-selective integrin-targeted therapies for inflammatory bowel disease.
J Crohns Colitis. 2018 May 15;:
Authors: Lamb CA, O’Byrne S, Keir ME, Butcher EC
Integrins are cell surface receptors with bi-directional signaling 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 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 signaling, 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), as well as the non-gut selective anti-α4 integrin (natalizumab), will be discussed as well as novel targeting approaches using small molecules.
PMID: 29767705 [PubMed – as supplied by publisher]