Cell Trafficking Interference in Inflammatory Bowel Disease: Therapeutic Interventions Based on Basic Pathogenesis Concepts

Tamara Pérez-Jeldres, Christopher J. Tyler, Joshua D. Boyer, Thangaraj Karuppuchamy, Giorgos Bamias, Parambir S. Dulai, Brigid S. Boland, William J. Sandborn, Derek R. Patel, Jesús Rivera-Nieves*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effective alternative. With 2 currently approved drugs (ie, natalizumab, vedolizumab) and several others in phase 3 trials (eg, etrolizumab, ozanimod, anti-MAdCAM-1), the blockade of trafficking molecules has firmly emerged as a new therapeutic era for IBD. We discuss the targets that have been explored in clinical trials: chemokines and its receptors (eg, IP10, CCR9), integrins (eg, natalizumab, AJM300, vedolizumab, and etrolizumab), and its endothelial ligands (MAdCAM-1, ICAM-1). We also discuss a distinct strategy that interferes with lymphocyte recirculation by blocking lymphocyte egress from lymph nodes (small molecule sphingosine-phosphate receptor [S1PR] agonists: fingolimod, ozanimod, etrasimod, amiselimod). Strategies on the horizon include additional small molecules, allosteric inhibitors that specifically bind to the active integrin form and nanovectors that allow for the use of RNA interference in the quest to modulate pro-inflammatory leukocyte trafficking in IBD.

Original languageEnglish (US)
Pages (from-to)270-282
Number of pages13
JournalInflammatory bowel diseases
Volume25
Issue number2
DOIs
StatePublished - Jan 10 2019
Externally publishedYes

Keywords

  • colitis
  • Crohn's
  • gut homing
  • MAdCAM-1
  • sphingosine-1-phosphate
  • ulcerative colitis
  • α4β7 Integrin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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