Format

Send to

Choose Destination
J Crohns Colitis. 2018 Aug 22;12(suppl_2):S653-S668. doi: 10.1093/ecco-jcc/jjy060.

Gut-Selective Integrin-Targeted Therapies for Inflammatory Bowel Disease.

Author information

1
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
2
Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
3
Global Medical Affairs, Takeda Pharmaceuticals International AG, Zurich, Switzerland.
4
Genentech Research & Early Development, South San Francisco, CA, USA.
5
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
6
Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.

Abstract

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.

PMID:
29767705
DOI:
10.1093/ecco-jcc/jjy060
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center