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Silencing invariant chain of DCs enhances Th1 response using small interfering RNA.

机译:沉默的DC恒定链可使用小分子干扰RNA增强Th1反应。

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摘要

RNA interference (RNAi), which causes the degradation of any RNA in a sequence specific manner, is a posttranscriptional gene silencing mechanism. Targeting the invariant chain (Ii) in DCs has been used as an approach to enhance antitumor immunity. It is demonstrated in this article that transfection of H-2(K) DCs with siRNA specific for Ii gene can significantly knock down Ii. When exposed to TNF-alpha, immature DCs transfected with Ii siRNA can differentiate into mature DCs without reducing viability or IL-12p70 production. Ii siRNA-treated H-2(K) DCs exhibited an increased allostimulatory capacity in a lymphocyte proliferation assay. Furthermore, Ii siRNA-transfected H-2(K) DCs enhanced Th1 responses by increasing IFN-gamma and decreasing IL-4 production, and much stronger cytotoxic activity was observed when DCs were co-transfected with Ii siRNA and an endogenous tumor antigen in vitro. Our findings indicate that silencing the Ii gene in DCs with siRNA may offer a potential approach to enhancing antitumor immunotherapy.
机译:RNA干扰(RNAi)是转录后基因沉默的机制,它以序列特异性的方式引起任何RNA的降解。针对DC中的恒定链(Ii)已被用作增强抗肿瘤免疫性的方法。本文证明,用对Ii基因具有特异性的siRNA转染H-2(K)DC可以显着降低Ii。当暴露于TNF-α时,用Ii siRNA转染的未成熟DC可以分化为成熟的DC,而不会降低生存力或IL-12p70的产生。 siRNA处理的H-2(K)DC在淋巴细胞增殖试验中显示出更高的同种刺激能力。此外,Ii siRNA转染的H-2(K)DC通过增加IFN-γ和降低IL-4产量来增强Th1反应,并且当DC与Ii siRNA和内源性肿瘤抗原共转染时,观察到更强的细胞毒性。体外。我们的发现表明,用siRNA沉默DC中的Ii基因可能为增强抗肿瘤免疫疗法提供了一种潜在的方法。

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