PMID- 19684160
OWN - NLM
STAT- MEDLINE
DCOM- 20091209
LR  - 20231213
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 21
IP  - 10
DP  - 2009 Oct
TI  - A novel approach to induce human DCs from monocytes by triggering 4-1BBL reverse 
      signaling.
PG  - 1135-44
LID - 10.1093/intimm/dxp077 [doi]
AB  - Dendritic cells (DCs) are responsible for the initiation of immune responses. Our 
      study demonstrates a new pathway for generating a large quantity of stimulatory 
      monocyte-derived DCs (Mo-DCs) from human monocytes using anti-4-1BB ligand 
      (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven Mo-DCs 
      (DCs(alpha-4-1BBL)) not only express higher levels of CD86, CD83 and HLA-DR, when 
      compared with the Mo-DCs matured by tumor necrosis factor alpha, but also exhibit 
      a unique phenotype that expresses lower levels of PD-L1. High levels of GM-CSF, 
      M-CSF and Flt3 ligand (FL) were found in the anti-4-1BBL-differentiation culture. 
      Neutralizing M-CSF, GM-CSF and FL inhibited Mo-DC proliferation stimulated by 
      anti-4-1BBL mAb, suggesting that M-CSF, GM-CSF and FL are involved in cell 
      proliferation stimulated by anti-4-1BBL. Further analysis of the 
      DCs(alpha-4-1BBL) showed increased secretion of T(h)1-type cytokines IL-12 and 
      IFN-gamma and decreased secretion of IL-10. DCs(alpha-4-1BBL) induced much 
      stronger proliferative responses in the mixed lymphocyte reaction assay when 
      compared with DCs derived by GM-CSF. Moreover, DCs(alpha-4-1BBL) preferentially 
      induced T(h)1 responses. We have further demonstrated that anti-4-1BBL antibody 
      stimulated nuclear translocation of NF-kappaB from the cytoplasm in monocytes, 
      suggesting that reverse signaling by 4-1BBL is likely responsible for mediating 
      DC differentiation. Collectively, we have found that reverse signaling of 4-1BBL 
      promotes the differentiation of potent T(h)1-inducing DCs from human monocytes.
FAU - Ju, Songwen
AU  - Ju S
AD  - Biotechnology Institute, Soochow University, Suzhou, Jiangsu Province, People's 
      Republic of China.
FAU - Ju, Songguang
AU  - Ju S
FAU - Ge, Yan
AU  - Ge Y
FAU - Qiu, Hongxia
AU  - Qiu H
FAU - Lu, Binfeng
AU  - Lu B
FAU - Qiu, Yuhua
AU  - Qiu Y
FAU - Fu, Jingxiang
AU  - Fu J
FAU - Liu, Gaoqin
AU  - Liu G
FAU - Wang, Qin
AU  - Wang Q
FAU - Hu, Yumin
AU  - Hu Y
FAU - Shu, Yongqian
AU  - Shu Y
FAU - Zhang, Xueguang
AU  - Zhang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090814
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (4-1BB Ligand)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (IL10 protein, human)
RN  - 0 (Immunoglobulins)
RN  - 0 (Immunologic Factors)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - 4-1BB Ligand/agonists/*immunology/metabolism
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antigens, CD/immunology/metabolism
MH  - B7-2 Antigen/immunology/metabolism
MH  - B7-H1 Antigen
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Proliferation/drug effects
MH  - Dendritic Cells/drug effects/*immunology/metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/immunology/metabolism
MH  - HLA-DR Antigens/immunology/metabolism
MH  - Humans
MH  - Immunoglobulins/immunology/metabolism
MH  - Immunologic Factors/*pharmacology
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-10/immunology/metabolism
MH  - Interleukin-12/immunology/metabolism
MH  - Macrophage Colony-Stimulating Factor/immunology/metabolism
MH  - Membrane Glycoproteins/immunology/metabolism
MH  - Monocytes/drug effects/*immunology/metabolism
MH  - NF-kappa B/immunology/metabolism
MH  - Signal Transduction/drug effects/immunology
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism
MH  - fms-Like Tyrosine Kinase 3/immunology/metabolism
MH  - CD83 Antigen
EDAT- 2009/08/18 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/08/18 09:00
PHST- 2009/08/18 09:00 [entrez]
PHST- 2009/08/18 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - dxp077 [pii]
AID - 10.1093/intimm/dxp077 [doi]
PST - ppublish
SO  - Int Immunol. 2009 Oct;21(10):1135-44. doi: 10.1093/intimm/dxp077. Epub 2009 Aug 
      14.