RRC ID 56701
Author Camara A, Cordeiro OG, Alloush F, Sponsel J, Chypre M, Onder L, Asano K, Tanaka M, Yagita H, Ludewig B, Flacher V, Mueller CG.
Title Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche.
Journal Immunity
Abstract Tissue-resident macrophages are receptive to specific signals concentrated in cellular niches that direct their cell differentiation and maintenance genetic programs. Here, we found that deficiency of the cytokine RANKL in lymphoid tissue organizers and marginal reticular stromal cells of lymph nodes resulted in the loss of the CD169+ sinusoidal macrophages (SMs) comprising the subcapsular and the medullary subtypes. Subcapsular SM differentiation was impaired in mice with targeted RANK deficiency in SMs. Temporally controlled RANK removal in lymphatic endothelial cells (LECs) revealed that lymphatic RANK activation during embryogenesis and shortly after birth was required for the differentiation of both SM subtypes. Moreover, RANK expression by LECs was necessary for SM restoration after inflammation-induced cell loss. Thus, cooperation between mesenchymal cells and LECs shapes a niche environment that supports SM differentiation and reconstitution after inflammation.
Volume 50(6)
Pages 1467-1481.e6
Published 2019-6-18
DOI 10.1016/j.immuni.2019.05.008
PII S1074-7613(19)30228-6
PMID 31201093
MeSH Animals Biomarkers Cell Differentiation Cellular Microenvironment Cytokines / metabolism* Immunophenotyping Lymph Nodes / cytology* Macrophages / immunology Macrophages / metabolism* Mesenchymal Stem Cells / metabolism* Mice Mice, Transgenic RANK Ligand / metabolism* Receptor Activator of Nuclear Factor-kappa B / metabolism* Signal Transduction Stromal Cells / metabolism*
IF 21.522
Times Cited 11
Mice RBRC06239