Zindl Carlene L, Kim Tea Hyun, Zeng Meiqin, Archambault Angela S, Grayson Mitchell H, Choi Kyunghee, Schreiber Robert D, Chaplin David D
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Immunity. 2009 Mar 20;30(3):408-20. doi: 10.1016/j.immuni.2009.01.010.
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.
淋巴毒素LTalpha(1)beta(2)支持脾脏结构多个方面的发育和维持，但其对边缘窦（MS）血管组织的意义尚不清楚。我们在此表明，在出生后早期缺乏淋巴毒素的小鼠中，发育中的Flk-1+白髓血管无法组织或上调黏膜地址素细胞黏附分子-1（MAdCAM-1），导致白髓内皮细胞和平滑肌肌动蛋白表达细胞的空间重排改变。在体外，MAdCAM-1指导在基质胶上生长的LTbeta受体+内皮细胞的重组。LTalpha(1)beta(2)还调节成年小鼠中MAdCAM-1表达和成熟MS结构的维持，对CD11b+细胞响应细菌抗原的正常运输起重要作用。总之，我们的研究表明，LTalpha(1)beta(2)和LTbeta受体信号控制成熟MS结构的正常发育和维持，并表明MAdCAM-1参与MS内皮细胞的结构形成，这对免疫细胞在脾脏内的移动很重要。
