title: Endothelial cell-specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation.
abstract: 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.
authors: Institute of Immunobiology, Kantonal Hospital St. Gallen, CH-9007 St. Gallen, Switzerland.
authors: Lucas
authors: L
authors: Onder
authors: Renzo
authors: R
authors: Danuser
authors: Elke
authors: E
authors: Scandella
authors: Sonja
authors: S
authors: Firner
authors: Qian
authors: Q
authors: Chai
authors: Thomas
authors: T
authors: Hehlgans
authors: Jens V
authors: JV
authors: Stein
authors: Burkhard
authors: B
authors: Ludewig
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D006706:Homeostasis; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology*; D053259:Lymphotoxin beta Receptor / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D019076:Transgenes; D014699:Venules / Q000502:physiology*
chemical_list: D015820:Cadherins; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor