CD11chi dendritic cells regulate the reestablishment of vascular quiescence and stabilization after immune stimulation of lymph nodes

摘要

Lymph node expansion during immune responses is accompanied by rapid vascular expansion. The reestablishment of quiescence and stabilization of the newly expanded vasculature and the regulatory mechanisms involved have not been well studied. We show that while initiation of vascular expansion in immune-stimulated nodes is associated with upregulated endothelial cell proliferation, increased high endothelial venule trafficking efficiency and VCAM-1 expression, and disrupted perivascular fibroblastic reticular cell organization, the reestablishment of vascular quiescence and stabilization after expansion is characterized by reversal of these phenomena. While CD11c^med cells are associated with the initiation of vascular expansion, CD11c^hiMHCII^med dendritic cells accumulate later and their short-term depletion in mice abrogates the reestablishment of vascular quiescence and stabilization. CD11c^hiMHCII^med cells promote endothelial cell quiescence in vitro and, in vivo, mediate quiescence at least in part by mediating reduced lymph node VEGF. Disrupted vascular quiescence and stabilization in expanded nodes is associated with attenuated T cell-dependent B cell responses. These results describe a novel mechanism whereby CD11c^hiMHCII^med dendritic cells regulate the reestablishment of vascular quiescence and stabilization after lymph node vascular expansion and suggest that these dendritic cells function in part to orchestrate the microenvironmental alterations required for successful immunity.