Regulation and implications of inflammatory lymphangiogenesis

Lymphatic vessels (LVs) are highly dynamic structures that intimately interact with their surrounding microenvironment. They have a profound influence on the immune system and therefore can manipulate inflammatory processes. Inflammation is a major cause of adulthood lymphangiogenesis and LV remodeling. In turn, LVs can reciprocally manipulate inflammatory processes. For instance, LV growth and/or activation regulate antigen presentation and inflammatory cell recruitment to lymph nodes (LNs), and therefore critically affect adaptive immunity. The vascular endothelial growth factor (VEGF)-C-VEGF receptor-3 and VEGF-A-VEGF receptor-2 signaling pathways are particularly important in inflammatory lymphangiogenesis. LVs contribute to the pathophysiology of various inflammatory conditions. Knowledge of lymphatic biology can be applied to manipulate inflammatory disorders and divert immune responses. This review summarizes basic concepts of inflammation-relevant lymphatic biology, and describes recent progress and practical implications.