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 under...

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Bibliographic Details
Published in:	The Journal of experimental medicine Vol. 203; no. 8; pp. 1903 - 1913
Main Authors:	Webster, Brian, Ekland, Eric H, Agle, Lucila M, Chyou, Susan, Ruggieri, Regina, Lu, Theresa T
Format:	Journal Article
Language:	English
Published:	United States The Rockefeller University Press 07-08-2006
Subjects:	Animals Blood Vessels - growth & development CD11c Antigen - immunology Cell Proliferation Dendritic Cells - physiology Endothelial Cells - cytology Homeodomain Proteins - metabolism Immunization Lymph Nodes - blood supply Lymph Nodes - cytology Lymphatic Vessels - cytology Lymphocytes - immunology Mice Mice, Inbred C57BL Vascular Endothelial Growth Factor A - metabolism
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Abbreviations used: DT, diphtheria toxin; DTR, DT receptor; HEV, high endothelial venule; VEGF, vascular endothelial growth factor. B. Webster and E.H. Ekland contributed equally to this paper. CORRESPONDENCE Theresa Lu: lut@hss.edu
ISSN:	0022-1007 1540-9538 1892-1007
DOI:	10.1084/jem.20052272