Lipopolysaccharide-induced Maturation of Bone Marrow-derived Dendritic Cells Is Regulated by Notch Signaling through the Up-regulation of CXCR4

Abstract

Dendritic cells (DCs) are professional antigen presenting cells to initiate immune response against pathogens, but mechanisms controlling the maturation of DCs are unclear. Here we report that, in the absence of recombination signal binding protein-Jkappa (RBP-J, the transcription factor mediating Notch signaling), lipopolysaccharide-stimulated monocyte-derived DCs are arrested at a developmental stage with few dendrites, low major histocompatibility complex II (MHC II) expression, and reduced motility and antigen presentation ability. RBP-J null DCs had lower expression of CXCR4. Transduction with a CXCR4-expressing lentivirus rescued developmental arrest of RBP-J-deficient DCs. Activation of Notch signaling in DCs up-regulated CXCR4 expression and increased the outgrowth of dendrites and the expression of MHC II. These effects were abrogated by a CXCR4 inhibitor. Therefore, Notch signaling is essential for DCs to transit from a dendrite(low)MHC II(low) immature state into a dendrite(high)MHC II(high) mature state, during the lipopolysaccharide-induced DC maturation, most likely through the up-regulation of CXCR4.