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Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche

Journal Paper/Review - Jun 11, 2019

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Citation
Camara A, Flacher V, Ludewig B, Yagita H, Tanaka M, Asano K, Onder L, Chypre M, Sponsel J, Alloush F, Cordeiro O, Mueller C. Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche. Immunity 2019; 50:1467-1481.e6.
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Journal Paper/Review (English)
Journal
Immunity 2019; 50
Publication Date
Jun 11, 2019
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Issn Electronic
1097-4180
Pages
1467-1481.e6
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Brief description/objective

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.