Lipopolysaccharide-induced maturation of bone marrow-derived dendritic cells is regulated by notch signaling through the up-regulation of CXCR4.
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.
State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China.
Yao-Chun
YC
Wang
Xing-Bin
XB
Hu
Fei
F
He
Fan
F
Feng
Lin
L
Wang
Wei
W
Li
Ping
P
Zhang
Duan
D
Li
Zhan-Sheng
ZS
Jia
Ying-Min
YM
Liang
Hua
H
Han
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002633:Chemotaxis; D017931:DNA Primers; D004251:DNA Transposable Elements / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
C514936:CXCR4 protein, mouse; D017931:DNA Primers; D004251:DNA Transposable Elements; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D019718:Receptors, CXCR4