Inhibition of endogenous MHC class II-restricted antigen presentation by tacrolimus (FK506) via FKBP51
Inhibition of endogenous MHC class II-restricted antigen presentation by tacrolimus (FK506) via FKBP51
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DOI：
10.1002/eji.200636392
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Sato, Noriyuki
中科院分区：
文献类型：
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作者：
Imai, Akihito;Sahara, Hiroeki;Sato, Noriyuki
他克莫司（FK 506）对T细胞产生IL-2的下调作用被认为是其强烈抑制免疫事件的主要原因。在这项研究中，我们表明，FK 506也有影响抗原呈递细胞在体外的抗原呈递。FK 506能够在体外抑制原代树突状细胞（DC）中内源性MHC II类限制性次要组织相容性抗原的呈递，但环孢素A（CsA）和雷帕霉素（RAP）不能。RNA干扰（RNAi）介导的内源性FK 506结合蛋白（FKBP）51表达的降低导致抗原呈递显著降低，表明FKBP 51在内源性MHC II类限制性抗原呈递中发挥作用。由于我们的模型使用了原代DC中天然表达的胞质抗原，这些效应可能是由于免疫抑制药物的新特性，并可能使我们能够阐明FK 506免疫抑制机制的新范式。
The effect of tacrolimus (FK506) on down-regulation of IL-2 production by T cells is considered to be mainly responsible for its strong suppression of immunological events. In this study, we show that FK506 also has an affect on antigen presentation by antigen-presenting cells in vitro. FK506 was able to inhibit the presentation of endogenous MHC class II-restricted minor histocompatibility antigens in primary dendritic cells (DC) in vitro, but cyclosporine A (CsA) and rapamycin (RAP) were not. RNA interference (RNAi)-mediated reduction of endogenous FK506-binding protein (FKBP)51 expression resulted in a marked decrease in antigen presentation, suggesting that FKBP51 plays a role in endogenous MHC class II-restricted antigen presentation. Since our model used naturally expressed cytosolic antigens in primary DC, these effects might have been due to novel properties of the immunosuppressive drugs and may allow us to elucidate a new paradigm for the immunosuppressive mechanism of FK506.