BBB seminar: Cornelia Halin
New insights into the immune and drainage functions of lymphatic vessels
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland
Lymphatic vessels are important for tissue fluid homeostasis and for the uptake of dietary lipids in the intestine. Moreover, by transporting antigen, inflammatory mediators, and leukocytes from peripheral tissues to draining lymph nodes, they are intimately linked with the induction of immune responses. Research during the last 10 years has revealed that lymphatic vessels form a highly plastic network, which rapidly adapts to inflammation in a stimulus- and tissue-specific manner. Inflammatory changes in the lymphatic network have been shown to impact fluid drainage as well as leukocyte trafficking, suggesting that lymphatic vessels play an active role in the regulation of inflammatory and immune responses. Performing a microarray analysis of lymphatic endothelial cells (LECs) isolated from inflamed and resting murine skin our group has recently generated a comprehensive description of the in vivo inflammatory response of LECs. Guided by these gene expression data we have started to investigate the involvement of various genes with previously unknown expression in LECs in lymphatic vessel biology. For example, we have identified a role for the interleukin-7 signaling pathway in lymphangiogenesis and in lymphatic drainage function. Our group has also recently established an intravital microscopy (IVM) model in the murine ear skin to image dendritic cell (DC) migration into and within afferent lymphatic vessels. Performing IVM we found that DCs actively migrate and patrol within initial lymphatic capillaries and are only passively propagated by lymph, in direction of the draining lymph node, once they reach larger collecting vessels. We could identify a first molecule involved in intralymphatic DC migration, namely the Rho-associated protein kinase. In our ongoing work we are further elucidating the mechanism and the functional significance of leukocyte migration through afferent lymphatic vessels. For example, our recent findings reveal that the LEC-expressed chemokine CCL21 orchestrates intralymphatic DC migration in downstream direction of the draining lymph node. Moreover, we have started to extend our IVM experiments to lymph-borne T cells and have found that they display a similar intralymphatic patrolling behavior as DCs within afferent lymphatic vessels.
Chairperson: Helge Wiig, Department of Biomedicine