The Lymphotoxin LTα1β2 Controls Postnatal and Adult Spleen Marginal Sinus Vascular Structure and Function

Carlene L. Zindl, Tea Hyun Kim, Meiqin Zeng, Angela S. Archambault, Mitchell H. Grayson, Kyunghee Choi, Robert D. Schreiber, David D. Chaplin

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)408-420
Number of pages13
JournalImmunity
Volume30
Issue number3
DOIs
StatePublished - Mar 20 2009

Keywords

  • CELLIMMUNO

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