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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.
This article was published in the following journal.
Name: Journal of Crohn's & colitis
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An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)
A species of Faecalbacterium, previously classified in the FUSOBACTERIUM genus, that is a major constituent of the GUT MICROBIOTA in healthy humans. It has anti-inflammatory activity and reduced numbers of this species occur in patients with INFLAMMATORY BOWEL DISEASES such as CROHN DISEASE.
An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
A humanized monoclonal immunoglobulin G4 antibody to human INTEGRIN ALPHA4 that binds to the alpha4 subunit of INTEGRIN ALPHA4BETA1 and integrin alpha4beta7. It is used as an IMMUNOLOGIC FACTOR in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS and CROHN'S DISEASE.
Astroesophageal Reflux Disease (GERD) Barrett's Esophagus Celiac Disease Cholesterol Crohn's Disease Gastroenterology Hepatitis Hepatology Irritable Bowel Syndrome (IBS) Pancreatitis Peptic Ulcer Disease...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...