Silencing c-Kit expression in human DCs suppresses Th2, Th17 response but enhances Th1 response.
Silencing c-Kit expression in human DCs suppresses Th2, Th17 response but enhances Th1 response.
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沉默人类 DC 中的 c-Kit 表达会抑制 Th2、Th17 反应，但会增强 Th1 反应。
DOI：
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发表时间：
2015-09
影响因子：
2.2
通讯作者：
Tong, Hui
中科院分区：
文献类型：
--
作者：
Huang, Qianchuan;Yan, Hongbo;Sun, Ting;Tong, Hui
树突状细胞（DC）是辅助性T细胞分化为辅助性T细胞1型TH 1、TH 2和TH 17亚群的组成部分。RNA干扰（RNA interference，RNAi）是一种转录后基因沉默机制，它以序列特异性方式降解任何RNA。靶向DC中的c-Kit已被用作增强抗肿瘤免疫的方法。本研究表明，c-Kit基因特异性siRNA转染DC后，可显著下调c-Kit基因表达。当暴露于TNF-α时，用c-Kit siRNA转染的未成熟DC可以分化为成熟DC而不降低活力或IL-12 p70产生。在淋巴细胞增殖试验中，c-Kit siRNA处理的DC表现出增加的同种异体刺激能力。此外，c-Kit siRNA转染的DC通过增加IFN-γ和减少IL-4的产生而增强TH 1应答，并且当DC与c-Kit siRNA和内源性肿瘤抗原共转染时观察到更强的体外细胞毒活性。我们的研究结果表明，沉默c-Kit基因在DC与siRNA可能提供一个潜在的方法，以提高抗肿瘤免疫治疗。
Dendritic cells (DCs) are integral to the differentiation of T helper cells into T helper type 1 TH1, TH2 and TH17 subsets. RNA interference (RNAi), which causes the degradation of any RNA in a sequence specific manner, is a posttranscriptional gene silencing mechanism. Targeting the c-Kit in DCs has been used as an approach to enhance antitumor immunity. Here, we shwed that transfection of DCs with siRNA specific for c-Kit gene can significantly knock down c-Kit. When exposed to TNF-α, immature DCs transfected with c-Kit siRNA can differentiate into mature DCs without reducing viability or IL-12p70 production. The c-Kit siRNA-treated DCs exhibited an increased allostimulatory capacity in a lymphocyte proliferation assay. Furthermore, c-Kit siRNA-transfected DCs enhanced TH1 responses by increasing IFN-γ and decreasing IL-4 production, and much stronger cytotoxic activity was observed when DCs were co-transfected with c-Kit siRNA and an endogenous tumor antigen in vitro. Our findings indicate that silencing the c-Kit gene in DCs with siRNA may offer a potential approach to enhance antitumor immunotherapy.
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影响因子：
32.4
作者：
Diefenbach, Andreas;Colonna, Marco;Koyasu, Shigeo
通讯作者：
Koyasu, Shigeo
影响因子：
13.8
作者：
Judson, Marc A.;Marchell, Richard M.;Brodmerkel, Carrie
通讯作者：
Brodmerkel, Carrie
影响因子：
64.5
作者：
Zamore, PD;Tuschl, T;Bartel, DP
通讯作者：
Bartel, DP
DOI：
10.1172/jci21102
发表时间：
2004-08
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
C. Borg;M. Terme;J. Taïeb;C. Ménard;C. Flament;C. Robert;K. Maruyama;H. Wakasugi;E. Angevin;K. Thielemans;A. Le Cesne;Veronique Chung-Scott;V. Lazar;I. Tchou;F. Crépineau;F. Lemoine;J. Bernard;J. Fletcher;A. Turhan;J. Blay;A. Spatz;J. Emile;M. Heinrich;S. Mécheri;T. Tursz;L. Zitvogel
通讯作者：
C. Borg;M. Terme;J. Taïeb;C. Ménard;C. Flament;C. Robert;K. Maruyama;H. Wakasugi;E. Angevin;K. Thielemans;A. Le Cesne;Veronique Chung-Scott;V. Lazar;I. Tchou;F. Crépineau;F. Lemoine;J. Bernard;J. Fletcher;A. Turhan;J. Blay;A. Spatz;J. Emile;M. Heinrich;S. Mécheri;T. Tursz;L. Zitvogel
影响因子：
15.3
作者：
Toes, R E;Ossendorp, F;Offringa, R;Melief, C J
通讯作者：
Melief, C J