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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2009-9-25
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-1BB Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD274,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD86,
http://linkedlifedata.com/resource/pubmed/chemical/CD274 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CD83 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/FLT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-DR Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/IL10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunologic Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/fms-Like Tyrosine Kinase 3
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1460-2377
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pubmed:author |
pubmed-author:FuJingxiangJ,
pubmed-author:GeYanY,
pubmed-author:HuYuminY,
pubmed-author:JuSongguangS,
pubmed-author:JuSongwenS,
pubmed-author:LiuGaoqinG,
pubmed-author:LuBinfengB,
pubmed-author:QiuHongxiaH,
pubmed-author:QiuYuhuaY,
pubmed-author:ShuYongqianY,
pubmed-author:WangQinQ,
pubmed-author:ZhangXueguangX
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pubmed:issnType |
Electronic
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1135-44
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19684160-4-1BB Ligand,
pubmed-meshheading:19684160-Antibodies, Monoclonal,
pubmed-meshheading:19684160-Antigens, CD,
pubmed-meshheading:19684160-Antigens, CD274,
pubmed-meshheading:19684160-Antigens, CD86,
pubmed-meshheading:19684160-Cell Differentiation,
pubmed-meshheading:19684160-Cell Proliferation,
pubmed-meshheading:19684160-Dendritic Cells,
pubmed-meshheading:19684160-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:19684160-HLA-DR Antigens,
pubmed-meshheading:19684160-Humans,
pubmed-meshheading:19684160-Immunoglobulins,
pubmed-meshheading:19684160-Immunologic Factors,
pubmed-meshheading:19684160-Interferon-gamma,
pubmed-meshheading:19684160-Interleukin-10,
pubmed-meshheading:19684160-Interleukin-12,
pubmed-meshheading:19684160-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:19684160-Membrane Glycoproteins,
pubmed-meshheading:19684160-Monocytes,
pubmed-meshheading:19684160-NF-kappa B,
pubmed-meshheading:19684160-Signal Transduction,
pubmed-meshheading:19684160-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19684160-fms-Like Tyrosine Kinase 3
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pubmed:year |
2009
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pubmed:articleTitle |
A novel approach to induce human DCs from monocytes by triggering 4-1BBL reverse signaling.
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pubmed:affiliation |
Biotechnology Institute, Soochow University, Suzhou, Jiangsu Province, People's Republic of China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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