CD169+macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling

Abstract

SignificanceThe 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.