Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL.
Fiche publication
Date publication
janvier 2016
Journal
PloS one
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MUELLER Christopher
Tous les auteurs :
Cordeiro OG, Chypre M, Brouard N, Rauber S, Alloush F, Romera-Hernandez M, Bénézech C, Li Z, Eckly A, Coles MC, Rot A, Yagita H, Léon C, Ludewig B, Cupedo T, Lanza F, Mueller CG
Lien Pubmed
Résumé
Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+ LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+ LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+ LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin.
Mots clés
Animals, Cells, Cultured, Endothelial Cells, cytology, Fibronectins, immunology, Lymph Nodes, cytology, Lymphotoxin-beta, immunology, Mice, Inbred C57BL, Platelet Membrane Glycoprotein IIb, immunology, RANK Ligand, immunology, Signal Transduction
Référence
PLoS One. 2016 ;11(3):e0151848