Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation.

Publication

Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation.

Journal Paper/Review - Feb 18, 2013

Onder Lucas, Danuser Renzo, Scandella Elke, Firner Sonja, Chai Qian, Hehlgans Thomas, Stein Jens V, Ludewig Burkhard

Citation

Onder L, Danuser R, Scandella E, Firner S, Chai Q, Hehlgans T, Stein J, Ludewig B. Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation. J Exp Med 2013; 210:465-73.

Type

Journal Paper/Review (English)

Journal

J Exp Med 2013; 210

Publication Date

Feb 18, 2013

Issn Electronic

1540-9538

Pages

465-73

Brief description/objective

The development of lymph nodes (LNs) and formation of LN stromal cell microenvironments is dependent on lymphotoxin-β receptor (LTβR) signaling. In particular, the LTβR-dependent crosstalk between mesenchymal lymphoid tissue organizer and hematopoietic lymphoid tissue inducer cells has been regarded as critical for these processes. Here, we assessed whether endothelial cell (EC)-restricted LTβR signaling impacts on LN development and the vascular LN microenvironment. Using EC-specific ablation of LTβR in mice, we found that conditionally LTβR-deficient animals failed to develop a significant proportion of their peripheral LNs. However, remnant LNs showed impaired formation of high endothelial venules (HEVs). Venules had lost their cuboidal shape, showed reduced segment length and branching points, and reduced adhesion molecule and constitutive chemokine expression. Due to the altered EC-lymphocyte interaction, homing of lymphocytes to peripheral LNs was significantly impaired. Thus, this study identifies ECs as an important LTβR-dependent lymphoid tissue organizer cell population and indicates that continuous triggering of the LTβR on LN ECs is critical for lymphocyte homeostasis.