Coordinated regulation of lymph node vascular-stromal growth first by CD11c+ cells and then by T and B cells

Item Type:	Article
Title:	Coordinated regulation of lymph node vascular-stromal growth first by CD11c+ cells and then by T and B cells
Creators Name:	Chyou, S. and Benahmed, F. and Chen, J. and Kumar, V. and Tian, S. and Lipp, M. and Lu, T.T.
Abstract:	Lymph node blood vessels play important roles in the support and trafficking of immune cells. The blood vasculature is a component of the vascular-stromal compartment that also includes the lymphatic vasculature and fibroblastic reticular cells (FRCs). During immune responses as lymph nodes swell, the blood vasculature undergoes a rapid proliferative growth that is initially dependent on CD11c(+) cells and vascular endothelial growth factor (VEGF) but is independent of lymphocytes. The lymphatic vasculature grows with similar kinetics and VEGF dependence, suggesting coregulation of blood and lymphatic vascular growth, but lymphatic growth has been shown to be B cell dependent. In this article, we show that blood vascular, lymphatic, and FRC growth are coordinately regulated and identify two distinct phases of vascular-stromal growth-an initiation phase, characterized by upregulated vascular-stromal proliferation, and a subsequent expansion phase. The initiation phase is CD11c(+) cell dependent and T/B cell independent, whereas the expansion phase is dependent on B and T cells together. Using CCR7(-/-) mice and selective depletion of migratory skin dendritic cells, we show that endogenous skin-derived dendritic cells are not important during the initiation phase and uncover a modest regulatory role for CCR7. Finally, we show that FRC VEGF expression is upregulated during initiation and that dendritic cells can stimulate increased fibroblastic VEGF, suggesting the scenario that lymph node-resident CD11c(+) cells orchestrate the initiation of blood and lymphatic vascular growth in part by stimulating FRCs to upregulate VEGF. These results illustrate how the lymph node microenvironment is shaped by the cells it supports.
Keywords:	CD11c Antigens, B-Lymphocytes, Cell Separation, Cellular Microenvironment, Leukocyte Chemotaxis, Dendritic Cells, Endothelial Cells, Fibroblasts, Flow Cytometry, Lymph Nodes, Lymphatic Vessels, NIH 3T3 Cells, T-Lymphocytes, Vascular Endothelial Growth Factor A, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	187
Number:	11
Page Range:	5558-5567
Date:	2 December 2011
Official Publication:	https://doi.org/10.4049/jimmunol.1101724
PubMed:	View item in PubMed

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