PROJECT SUMMARY/ABSTRACT
Anti-integrin a4ß7 therapy (vedolizumab) has demonstrated outstanding safety and efficacy for the treatment of
inflammatory bowel disease (IBD), a relatively common, chronic, incurable pair of idiopathic immune-mediated
diseases of the intestines (Crohn’s disease and ulcerative colitis) that typically strike in youth to early adulthood
to produce lifelong suffering and disability. However, for unknown reasons, many IBD patients do not respond
to even this therapy. We recently generated evidence that this therapy selectively affects the intestinal
migration of dendritic cells (DC) rather than T cells, as had been widely presumed. We therefore seek to
demonstrate that directly observing the nature of these DC, and their response to vedolizumab, will improve
our currently limited clinical tools for predicting and optimizing the efficacy of this therapy. Additionally, by
demonstrating that DC are the actual target of this profoundly specific yet effective therapy, we have implicated
them directly in the pathogenesis of IBD, which to date remains poorly understood. We therefore propose to
perform a detailed analysis on DC from the blood and colonic mucosa of IBD patients to correlate their
phenotype and diversity with the presence or absence of inflammation, and more specifically how vedolizumab
induces remission in IBD. By doing so, we will not only improve our existing tools for helping IBD patients, but
also reveal for new strategies to treat or even cure this significant public health problem.