The Functional Unit of the Lymphatic System: Towards Understanding the Importance of a Well-Rehearsed Interaction of Lymphatic Capillaries, Collecting Vessels, and Lymph Nodes.

Introduction: Lymphatic vessels and lymph nodes (LNs) are part of the lymphatic system taking care of interstitial tissue homoeostasis, lipid transport, and immune response. The interposition of LNs in between the lymphatic vasculature allows the filtration of lymph fluid, cell-cell interactions, and also the transfer of lymph fluid into the venous system. An important role of lymphatic flow, which is often underestimated, is the active involvement of lymph flow and the lymphatic vasculature in immunologic function.

Summary: The present review summarizes the current knowledge of the different functional units of the lymphatic transport system trying to create a model of their interplay and options to react to inflammatory conditions. Remodelling of the lymphatic system during inflammation includes lymphangiogenesis, changed fluid transport rates, and modification of LN morphology. Alterations of these processes can aggravate inflammatory processes, leading to an incomplete resolution of the inflammation and often ending in chronic inflammatory condition. Despite the development of histological markers to visualize lymphatic vessels, new imaging methods and increased knowledge about the different parts of the lymphatic system the general overview about the interplay of the different components is missing.

Key Messages: We show the importance of lymphatic flow in the initiation of the immune response and the solution of an inflammation. We speculate that the increase in density and vessel diameter of lymph vessels is necessary to increase the fluid influx, efflux and the migration of cells into the LN. A failure of antigen-tissue clearance leads to chronic inflammation. Remodelling of LN morphology and vasculature is also necessary in this reaction. An overrun of the defending capacity of the LN is prevented by the immune system via control of the lymph vessel transport capacity and LN remodelling.