Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells.
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.
Department of Gene and Cell Medicine, Graduate Program in Immunology and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029;
Emma L
EL
Kuan
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Stoyan
S
Ivanov
Division of Lymphatic Biology, Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Texas A&M Health Science Center College of Medicine, Temple, TX 76504;
Eric A
EA
Bridenbaugh
Program in Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, New York University School of Medicine, New York, NY 10016;
Gabriel
G
Victora
Division of Lymphatic Biology, Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Texas A&M Health Science Center College of Medicine, Temple, TX 76504;
Wei
W
Wang
Department of Surgery, Cardiovascular Research Institute, Texas A&M Health Science Center College of Medicine, Temple, TX 76504;
Ed W
EW
Childs
Department of Gene and Cell Medicine, Graduate Program in Immunology and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029;
Andrew M
AM
Platt
Department of Pediatrics, National Jewish Health, Denver, CO 80206;
Claudia V
CV
Jakubzick
Department of Medicine, National Jewish Health, Denver, CO 80206;
Robert J
RJ
Mason
Division of Lymphatic Biology, Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Texas A&M Health Science Center College of Medicine, Temple, TX 76504;
Anatoliy A
AA
Gashev
Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065; and.
Michel
M
Nussenzweig
Institute of Bioengineering, Swiss Federal Institute of Technology, Lausanne 1015, Switzerland.
Melody A
MA
Swartz
Program in Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, New York University School of Medicine, New York, NY 10016;
Michael L
http://orcid.org/0000-0003-4983-6389
ML
Dustin
Division of Lymphatic Biology, Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Texas A&M Health Science Center College of Medicine, Temple, TX 76504;
David C
DC
Zawieja
Department of Gene and Cell Medicine, Graduate Program in Immunology and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110; grandolph@path.wustl.edu.
Gwendalyn J
GJ
Randolph
D000273:Adipose Tissue / Q000276:immunology* / Q000473:pathology; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D042601:Lymphatic Vessels / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology; D019108:Tight Junctions / Q000276:immunology
D000949:Histocompatibility Antigens Class II