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

Publication

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

Camara Abdouramane, Flacher Vincent, Ludewig Burkhard, Yagita Hideo, Tanaka Masato, Asano Kenichi, Onder Lucas, Chypre Mélanie, Sponsel Janina, Alloush Farouk, Cordeiro Olga G, Mueller Christopher G

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.

Type

Journal Paper/Review (English)

Journal

Immunity 2019; 50

Publication Date

Jun 11, 2019

Issn Electronic

1097-4180

Pages

1467-1481.e6

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.