Immunosuppressive effects of the traditional Chinese herb Qu Mai on human alloreactive T cells.
Immunosuppressive effects of the traditional Chinese herb Qu Mai on human alloreactive T cells.
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DOI:
10.1111/ajt.12180
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发表时间:
2013-05
期刊:
影响因子:
--
通讯作者:
Heeger P
中科院分区:
文献类型:
--
作者:
Reid-Adam J;Yang N;Song Y;Cravedi P;Li XM;Heeger P
Current therapies for transplant rejection are sub-optimally effective. In an effort to discover novel immunosuppressants we used cytokine ELISPOT and ELISAs to screen extracts from 53 traditional Chinese herbs for their ability to suppress human alloreactive T cells. We identified a dichloromethane-soluble fraction (QMAD) of Qu Mai (Dianthus superbus) as a candidate. HPLC analysis of QMAD revealed 3 dominant peaks, each with a MW ~600 Daltons and distinct from cyclosporine and rapamycin. When we added QMAD to human mixed lymphocyte cultures, we observed dose-dependent inhibition of proliferation and IFNγ production, by naïve and memory alloreactive T cells, and observed an increased frequency of Foxp3+CD4+ T cells. To address whether QMAD induces regulatory T cells we added QMAD to anti-CD3/CD28-stimulated naïve CD4 T cells and observed a dose-dependent upregulation of Foxp3 associated with new suppressive capacity. Mechanistically, QMAD did not induce T cell IL-10 or TGFβ but blocked T cell AKT phosphorylation, a key signaling nexus required for T cell proliferation and expansion, that simultaneously prevents Foxp3 transcription. Our findings provide novel insight into the anti-inflammatory effects of one traditional Chinese herb, and support the need for continued isolation, characterization and testing of QMAD-derived components as immune suppressants for transplant rejection.
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