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PMID: 16831898 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of lymph node vascular growth by dendritic cells.

The Journal of experimental medicine ·Vol. 203 ·No. 8 ·2006-08-07 ·Pages 1903-13

Webster B, Ekland EH, Agle LM, Chyou S, Ruggieri R, Lu TT

Abstract

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.

MeSH Terms
Animals Blood Vessels/growth & development CD11c Antigen/immunology Cell Proliferation Dendritic Cells/physiology Endothelial Cells/cytology Homeodomain Proteins/metabolism Immunization Lymph Nodes/blood supply,cytology Lymphatic Vessels/cytology Lymphocytes/immunology Mice Mice, Inbred C57BL Vascular Endothelial Growth Factor A/metabolism
Chemicals
CD11c Antigen Homeodomain Proteins Vascular Endothelial Growth Factor A RAG-1 protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Webster Brian
Autoimmunity and Inflammation Program, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Ekland Eric H
Agle Lucila M
Chyou Susan
Ruggieri Regina
Lu Theresa T
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
2006-08-07
Epub
2006-00-10
Pages
1903-13
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118366
Subset
IM
Grants
NCRR NIH HHS · C06 RR012538 · United States
NIAID NIH HHS · T32 AI007621 · United States
NIAID NIH HHS · 5T32 AI007621-07 · United States
NCRR NIH HHS · C06-RR12538-01 · United States
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