Regulation of lymph node vascular growth by dendritic cells.
Lymph nodes grow rapidly and robustly at the initiation of an immune response, and this growth is accompanied by growth of the blood vessels. Although the vessels are critical for supplying nutrients and for controlling cell trafficking, the regulation of lymph node vascular growth is not well understood. We show that lymph node endothelial cells begin to proliferate within 2 d of immunization and undergo a corresponding expansion in cell numbers. Endothelial cell proliferation is dependent on CD11c+ dendritic cells (DCs), and the subcutaneous injection of DCs is sufficient to trigger endothelial cell proliferation and growth. Lymph node endothelial cell proliferation is dependent on vascular endothelial growth factor (VEGF), and DCs are associated with increased lymph node VEGF levels. DC-induced endothelial cell proliferation and increased VEGF levels are mediated by DC-induced recruitment of blood-borne cells. Vascular growth in the draining lymph node includes the growth of high endothelial venule endothelial cells and is functionally associated with increased cell entry into the lymph node. Collectively, our results suggest a scenario whereby endothelial cell expansion in the draining lymph node is induced by DCs as part of a program that optimizes the microenvironment for the ensuing immune response.
Webster
Brian
B
Autoimmunity and Inflammation Program, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Ekland
Eric H
EH
Agle
Lucila M
LM
Chyou
Susan
S
Ruggieri
Regina
R
Lu
Theresa T
TT
D000818:Animals; D001808:Blood Vessels / Q000254:growth & development*; D039521:CD11c Antigen / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000378:metabolism; D007114:Immunization; D008198:Lymph Nodes / Q000098:blood supply* / Q000166:cytology; D042601:Lymphatic Vessels / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D039521:CD11c Antigen; D018398:Homeodomain Proteins; D042461:Vascular Endothelial Growth Factor A; C064658:RAG-1 protein