國家衛生研究院 NHRI:Item 3990099045/7185
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    題名: Mesenchymal stem cells tune the development of monocyte-derived dendritic cells toward a myeloid-derived suppressive phenotype through growth-regulated oncogene chemokines
    作者: Chen, HW;Chen, HY;Wang, LT;Wang, FH;Fang, LW;Lai, HY;Chen, HH;Lu, J;Hung, MS;Cheng, Y;Chen, MY;Liu, SJ;Chong, P;Lee, OK;Hsu, SC
    貢獻者: Division of Vaccine Research and Development;Division of Infectious Diseases;Institute of Biotechnology and Pharmaceutical Research
    摘要: Mesenchymal stem/stromal cells (MSCs) are promising potential candidates for the treatment of immunological diseases because of their immunosuppressive functions. However, the molecular mechanisms that mediate MSCs' immunosuppressive activity remain elusive. In this article, we report for the first time, to our knowledge, that secreted growth-regulated oncogene (GRO) chemokines, specifically GRO-gamma, in human MSC-conditioned media have an effect on the differentiation and the function of human monocyte-derived dendritic cells. The monocyte-derived dendritic cells were driven toward a myeloid-derived suppressor cell (MDSC)-like phenotype by the GRO chemokines. GRO-gamma-treated MDSCs had a tolerogenic phenotype that was characterized by an increase in the secretion of IL-10 and IL-4, and a reduction in the production of IL-12 and IFN-gamma. We have also shown that the mRNA expression levels of the arginase-1 and inducible NO synthase genes, which characterize MDSCs, were upregulated by GRO-gamma-primed mouse bone marrow cells. In addition, the ability of GRO-gamma-treated bone marrow-derived dendritic cells to stimulate the OVA-specific CD8+ T (OT-1) cell proliferation and the cytokine production of IFN-gamma and TNF-alpha were significantly decreased in vivo. Our findings allow a greater understanding of how MDSCs can be generated and offer new perspectives to exploit the potential of MDSCs for alternative approaches to treat chronic inflammation and autoimmunity, as well as for the prevention of transplant rejection.
    日期: 2013-05
    關聯: Journal of Immunology. 2013 May;190(10):5065-5077.
    Link to: http://dx.doi.org/10.4049/jimmunol.1202775
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000318546700018
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84877836310
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