TY - JOUR
T1 - The Lymphotoxin LTα1β2 Controls Postnatal and Adult Spleen Marginal Sinus Vascular Structure and Function
AU - Zindl, Carlene L.
AU - Kim, Tea Hyun
AU - Zeng, Meiqin
AU - Archambault, Angela S.
AU - Grayson, Mitchell H.
AU - Choi, Kyunghee
AU - Schreiber, Robert D.
AU - Chaplin, David D.
PY - 2009/3/20
Y1 - 2009/3/20
N2 - The lymphotoxin LTα1β2 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 LTβ receptor+ endothelial cells grown on Matrigel. LTα1β2 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 LTα1β2 and LTβ 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.
AB - The lymphotoxin LTα1β2 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 LTβ receptor+ endothelial cells grown on Matrigel. LTα1β2 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 LTα1β2 and LTβ 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.
KW - CELLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=61949160618&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2009.01.010
DO - 10.1016/j.immuni.2009.01.010
M3 - Article
C2 - 19303389
AN - SCOPUS:61949160618
VL - 30
SP - 408
EP - 420
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -