Collecting Lymphatic Vessel Permeability Facilitates Adipose Tissue Inflammation and Distribution of Antigen to Lymph Node–Homing Adipose Tissue Dendritic Cells
Kuan EL., Ivanov S., Bridenbaugh EA., Victora G., Wang W., Childs EW., Platt AM., Jakubzick CV., Mason RJ., Gashev AA., Nussenzweig M., Swartz MA., Dustin ML., Zawieja DC., Randolph GJ.
Abstract Collecting lymphatic vessels (CLVs), surrounded by fat and endowed with contractile muscle and valves, transport lymph from tissues after it is absorbed into lymphatic capillaries. CLVs are not known to participate in immune responses. In this study, we observed that the inherent permeability of CLVs allowed broad distribution of lymph components within surrounding fat for uptake by adjacent macrophages and dendritic cells (DCs) that actively interacted with CLVs. Endocytosis of lymph-derived Ags by these cells supported recall T cell responses in the fat and also generated Ag-bearing DCs for emigration into adjacent lymph nodes (LNs). Enhanced recruitment of DCs to inflammation-reactive LNs significantly relied on adipose tissue DCs to maintain sufficient numbers of Ag-bearing DCs as the LN expanded. Thus, CLVs coordinate inflammation and immunity within adipose depots and foster the generation of an unexpected pool of APCs for Ag transport into the adjacent LN.