Scientific Abstract

Proposal No. IBD-0224R2
Principal Investigator:   Silvio Danese, M.D., Ph.D.
Applicant Organization:  Fondazione Humanitas per La Ricerca (Milan, Italy)
Project Title:  The role of lymphangiogenesis in inflammatory bowel disease pathogenesis
Period of Award:  April 1, 2008 – March 31, 2010

The lymphatic vasculature complements the blood vascular network and performs the unique function of transporting extravasated fluid unidirectionally from tissues back to the blood circulation. The lymphatic vasculature also plays a fundamental role in immunity. Indeed, lymphocytes and antigen-presenting cells enter the lymphatic capillaries in the periphery and migrate through the lymph nodes to elicit acquired immune responses. Wound healing, cancer, autoimmunity and chronic inflammatory diseases are all associated with blood angiogenesis. However, recent evidence suggests that robust lymphangiogenesis also occurs in these conditions, and particularly in chronically inflamed tissues, such as in the inflamed synovium, psoriatic skin, kidney transplant undergoing rejection, the intima of atherosclerotic lesions,  and the lung or corneal inflammation. Whether lymphangiogenesis also plays a role in the pathogenesis of IBD, and whether its blockade is beneficial in chronic intestinal inflammation remains to be determined.

In this project we propose to evaluate lymphangiogenesis in human and experimental colitis as a component of IBD pathogenesis. Furthermore, we propose to investigate the blockade of lymphangiogenesis as a novel therapeutic strategy for IBD.