CD169 <sup>+</sup> macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling
Abdouramane Camara, Alice C Lavanant, Jun Abe, Henri Lee Desforges, Yannick O. Alexandre, Erika Girardi, Zinaida Igamberdieva, Kenichi Asano, Masato Tanaka, Thomas Hehlgans, Klaus Pfeffer, Sébastien Pfeffer, Scott N. Mueller, Jens V. Stein, Christopher G. Mueller
Abstract
Significance The CD169 + macrophages that play an important role in the fight against infections and cancer are receptive to environmental signals for their differentiation. We show that lymph node and splenic CD169 + macrophages require both LTβR and RANK signaling since the conditional deficiency of either receptor results in their disappearance. Using a reporter mouse, we observe RANKL expression by a splenic mesenchymal cell subset and show that it participates in CD169 + macrophage differentiation. Their absence leads to a reduced viral capture and a greatly attenuated virus-specific CD8 + T cell expansion. Thus, tight control mechanisms operate for the precise positioning of these macrophages at sites where numerous immune-stimulatory forces converge.