Lymphangiogenesis not only occurs during embryonic development and tumor growth but also accompanies many chronic inflammatory conditions, such as psoriasis, rheumatoid arthritis or inflammatory bowel disease. Increasing evidence suggests that inflammation-induced changes in the lymphatic vasculature have a profound impact on the course of inflammatory and immune responses, by modulating fluid drainage, leukocyte migration or the removal of inflammatory mediators from tissues.

Our lab employs different mouse models of acute and persistent skin inflammation to better characterize the in vivo inflammatory response of the lymphatic vasculature. Our work has revealed that lymphangiogenesis is not limited to the inflamed tissue but also results in a dramatic expansion of the lymphatic network in draining lymph nodes (LN lymphangiogenesis). In a mouse model of contact hypersensitivity (CHS)-induced skin inflammation we observed that VEGF-A produced in the inflamed skin accounted for lymphangiogenesis in the inflamed skin and also in draining LNs. To investigate how skin inflammation and changes in the lymphatic network impact lymphatic function we performed lymphatic drainage and dendritic cell migration experiments in this model. These studies revealed that drainage was compromised during both acute and persistent inflammation, indicating that an inflammation-induced, proliferative enlargement of the lymphatic network does not necessarily lead to improved lymphatic vessel function. To better study the in vivo inflammatory response of lymphatic endothelial cells (LECs) we have recently performed a microarray-based analysis of LECs isolated from resting and inflamed skin. This analysis demonstrated that the inflammatory response of LECs is highly stimulus specific and results in differential up-regulation of chemokines and adhesion molecules, depending on the inflammatory stimulus applied. Guided by our microarray data we have also started to characterize genes with previously unknown expression in LECs for their role in lymphatic vessel formation, lymphangiogenesis and lymphatic function.