國家衛生研究院 NHRI:Item 3990099045/7120
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    题名: Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10(+)IFN-gamma(+)CD4(+) regulatory T cells to Control transplant arteriosclerosis
    其它题名: Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis
    作者: Hsu, WT;Lin, CH;Chiang, BL;Jui, HY;Wu, KKY;Lee, CM
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow-derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10(+) and IFN-gamma(+) cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10(+)IFN-gamma(+)CD4(+) regulatory T type 1 (T(R)1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10(+)IFN-gamma(+)CD4(+) cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble T(R)1-like cells. Both cyclooxygenase-derived PGE(2) and IDO help to induce T(R)1-like cells by MSCs. MSCs constitutively secrete PGE(2), which is augmented in allogeneic reactions. However, T(R)1-like cells were deficient in PGE(2) and 4-fold less potent than were MSCs in suppressing MLR. PGE(2) mimetic supplements can enhance the immunosuppressive potency of T(R)1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced T(R)1-like cells combined with PGE(2), but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: T(R)1-like cells + PGE(2): 11 +/- 10%; PGE(2) alone: 93 +/- 8.7%; T(R)1-like cells alone: 88 +/- 2.4% versus untreated 94 +/- 0.9%, p < 0.001). These findings indicate that PGE(2) helps MSC-induced IL-10(+)IFN-gamma(+)CD4(+) T(R)1-like cells inhibit TA. PGE(2) combined with MSC-induced TR1-like cells represents a new approach for achieving immune tolerance.
    日期: 2013-03-01
    關聯: Journal of Immunology. 2013 Mar 1;190(5):2372-2380.
    Link to: http://dx.doi.org/10.4049/jimmunol.1202996
    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:000315089100052
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84874239821
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