The lymphotoxin LTalpha(1)beta(2) controls postnatal and adult spleen marginal sinus vascular structure and function.
The lymphotoxin LTalpha(1)beta(2) supports the development and maintenance of several aspects of spleen structure, but its significance for marginal sinus (MS) vascular organization is unclear. We showed here that, in early postnatal lymphotoxin-deficient mice, the developing Flk-1+ white pulp vessels failed to organize or upregulate MAdCAM-1, leading to altered spatial rearrangement of both the white pulp endothelial cells and the smooth muscle actin-expressing cells. In vitro, MAdCAM-1 directed the reorganization of LTbeta receptor+ endothelial cells grown on Matrigel. LTalpha(1)beta(2) also regulated the maintenance of both MAdCAM-1 expression and mature MS structure in adult mice, contributing importantly to normal trafficking of CD11b+ cells in response to bacterial antigens. Together, our studies demonstrate that LTalpha(1)beta(2) and LTbeta receptor signals control proper development and maintenance of the mature MS structure and implicate MAdCAM-1 in the structuring of the MS endothelial cells that is important for the movement of immune cells within the spleen.
Zindl
Carlene L
CL
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kim
Tea Hyun
TH
Zeng
Meiqin
M
Archambault
Angela S
AS
Grayson
Mitchell H
MH
Choi
Kyunghee
K
Schreiber
Robert D
RD
Chaplin
David D
DD
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D000099152:Cadherin 5
D000942:Antigens, Bacterial; D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D009088:Mucoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5; C489082:Madcam1 protein, mouse