國家衛生研究院 NHRI:Item 3990099045/6889
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    题名: Overexpression of galectin-9 in islets prolongs grafts survival via downregulation of Th1 responses
    作者: Chou, FC;Kuo, CC;Wang, YL;Lin, MH;Yen, BL;Chang, DM;Sytwu, HK
    贡献者: Institute of Cellular and Systems Medicine
    摘要: The differential activation of T helper (Th) cells and production of cytokines contribute to graft rejection or tolerance. In general, the Th1-type cytokines and cytotoxic T cells are detected consistently in host undergoing rejection, whereas Th2 responses are linked to a tolerance condition. Galectin-9 modulates Th1 cell immunity by binding to the T-cell immunoglobulin mucin-3 (Tim-3) molecule expressed on the Th1 cells. We investigate whether overexpression of galectin-9 in islets prolongs grafts survival in diabetic recipients. Islets were transduced with lentiviruses carrying galectin-9 and were then transplanted to streptozotocin-induced diabetic NOD/SCID recipients. The normoglycemic recipients then received splenocytes from diabetic NOD mice. Blood glucose concentration was monitored daily after adoptive transfer. The histology of the islet grafts and flow cytometric analyses were assessed at the end of the study. Overexpression of galectin-9 in islets prolonged grafts survival in NOD/SCID mice after challenge with diabetogenic splenocytes (mean graft survival, 38.5 vs 26.0 days, n = 10, respectively; P = 0.0096). The galectin-9-overexpressed grafts showed decreased infiltration of IFN-gamma-producing CD4(+) and CD8(+) T cells, but not of IL-17-producing CD4(+) T cells. Strikingly, this islet-specific genetic manipulation did not affect the systemic lymphocyte composition, indicating that galectin-9 may regulate T cellmediated inflammation in situ. We demonstrate that galectin-9 protects grafts from Th1- and Tc1-cell-mediated rejections, suggesting that galectin-9 has preventive and/or therapeutic benefit in transplant therapy for autoimmune diabetes and may be applied further to the transplantation of other organs or tissues.
    日期: 2013-11
    關聯: Cell Transplant. 2013 Nov;22(11):2135-2145.
    Link to: http://dx.doi.org/10.3727/096368912x657891
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0963-6897&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000327109200014
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84886424649
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