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Targeting of gut specific leucocyte recruitment in IBD by vedolizumab
  1. Bertus Eksteen
  1. Correspondence to Dr Bertus Eksteen, Division of Gastroenterology and Hepatology, Snyder Institute for Chronic Diseases, Health Research and Innovation Centre (HRIC), University of Calgary, 4AC66—3280 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1; b.eksteen{at}ucalgary.ca

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IBD is characterised by an inappropriate immune response to our own gut microbiota in the setting of a genetically susceptible individual. The consequence of this dysregulated process is activation of the innate immune system which in turn produces cytokines such as tumour necrosis factor α (TNFα) and activation of the adaptive immune system with subsequent recruitment of pro-inflammatory T and B cells to the colon or small bowel. This in turn leads to further amplification of pro-inflammatory cytokines release which bind to cognate receptors and activation of intercellular pathway such as JAK and STAT to mediate tissue inflammation. The mainstay of treatment for individuals with moderate to severe disease UC or Crohn's disease has been therapeutic targeting of the pro-inflammatory cytokine, TNFα. Unfortunately, a significant proportion of individuals will be refractory to these medications or eventually lose efficacy. This has widened the search for other pathways that might be targeted to treat IBD. The most advanced of these treatments are the integrin inhibitors that target trafficking of lymphocytes to the gut.1

The maintenance of gut immunity is critically dependent on regional immune responses that are generated in the gut-associated lymphoid tissues. Dendritic cells (DCs) are positioned within the lamina propria in close relation to the enterocytes to continuously monitor the micro environment for potential antigens. Once an antigen is detected, gut DCs migrate to the mesenteric lymph nodes and the Peyer's patches. Within these secondary lymphoid tissues, DCs imprint on naive T and B cells’ knowledge of the antigen to generate an appropriate immune response. DC–lymphocyte priming conveys recognition of the antigen and the shape of the immune response required such as a …

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