ISSN: 2155-9899
Martina Vranova and Cornelia Halin
Lymphatic vessels are important for tissue fluid homeostasis and for the uptake of dietary lipids in the intestine. Moreover, lymphatic vessels are intimately linked with induction of the immune response, as they transport antigen, inflammatory mediators, and leukocytes from peripheral tissues to draining lymph nodes (dLNs). Research of 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. The inflammatory environment induces changes in gene expression in lymphatic endothelial cells (LECs) and leads to a profound proliferative expansion of the lymphatic network in both the inflamed tissue and the dLNs. 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 processes. In fact, experimentally enhancing or blocking lymphangiogenesis was shown to modulate the course of inflammatory and immune responses in various disease models. Given these exciting pre-clinical findings, lymphatic vessels and inflammatory lymphangiogenesis are emerging as potential new therapeutic targets for the treatment of chronic inflammatory and autoimmune disorders, and for the prevention of graft rejection. In this review, we will summarize current knowledge about the inflammatory response of the lymphatic network and introduce the main molecular and cellular mediators of inflammatory lymphangiogenesis. Our review will particularly focus on how inflammation-induced changes in lymphatic vessels are thought to impact the course of inflammatory and immune responses and address the therapeutic implications of these findings.