BBB Seminar: Dontscho Kerjaschki
The sunrise of understanding lymphatic vessel function in human diseases
Clinical Institute of Pathology, Medical University of Vienna, Austria
The lymphatic vasculature plays a major role in the homeostasis of extracellular fluids, salts and migrating cells, and is also involved in numerous diseases, ranging from metastasis to hypertension. Lymphatic endothelial cells (LEC) show distinct heterogeneous phenotypes and functional properties, depending on their anatomical localization in the vascular tree. As all vessels, also lymphatics are stabilized by pericytes. We found that attraction of pericyte precursors is regulated by the interaction of the lymphatic membrane sialomucin podoplanin, that is shed via exosomes, and binds and quenches platelet-derived growth factor (PDGF)-BB.
As an example for the phenotypic adaptation of LECs to metabolic disease we have analyzed the gene expression profiles of human type 2 diabetics, and compared it to that of normo-glycaemic controls. We found complex changes e.g. in the mRNA levels of lipid and ion transporters, chemokines, inflammatory and anti-infectious molecules etc. that all dovetail into the clinical presentation of long-term diabetics.
Lymphangiogenesis also plays a major role in human chronic inflammatory diseases, such as renal transplant rejection. We have found explosive lymph vessel growth with the arrival of the inflammatory rejection infiltrate, and provided evidence that these newly formed LECs organize typical tertiary lymphatic organs in the kidney. Unexpectedly, these infiltrates contain numerous regulatory T-lymphocytes that are attracted by chemokines produced by LECs and reduce the aggressively of the infiltrate.
Host: Helge Wiig , Department of Biomedicine