The ‘IN’ of chronic inflammation—that is, the mechanisms of cell entry into the intestinal mucosa, bacterial and foreign antigen invasion, angiogenesis, and the control of gut inflammation through intestinal microvasculature—has received a great deal of attention in studies of the pathogenesis of inflammatory bowel disease (IBD). This has resulted in the validation of several targets for the treatment of experimental inflammation—both on immune and non-immune cells—some of which have translated into effective treatments for patients with IBD. An important aspect of this has been our growing understanding of the role the intestinal vascular microcirculation plays in the initiation and perpetuation of the inflammatory process, by regulating the migration of leucocytes into the interstitial space. However, it is becoming increasingly clear that it is also important to focus on the ‘OUT’ of chronic inflammation—that is, the lymphatics and their role in controlling tissue oedema, leucocyte exit, bacterial antigen and inflammatory chemokine clearance. As our understanding of the lymphatics and the role they play grows, another rich source of non-immune cell targets for therapeutic intervention is gradually being revealed. This article describes current knowledge of the roles played by the vascular and lymphatic endothelium throughout the gut in the pathogenesis of IBD, and how this differs from their role under physiological conditions, as well as discussing current and future therapeutic targets that have been identified.
- Endothelial cells
- inflammatory bowel disease
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Funding The studies reported in this review were supported by grants from the Broad Medical Research Program, the Italian Ministry of Health (Ricerca Finalizzata 2006, n.72 and Bando Giovani Ricercatori), Fondazione Cariplo, the Italian Association for Cancer Research (my first AIRC Grant and IG 10205) and AMICI Italia to SD. This work was conducted in the context, and with the support, of the Fondazione Humanitas per la Ricerca (Rozzano, Italy).
Competing interest None.
Provenance and peer review Commissioned; externally peer reviewed.
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