A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation.
A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation.
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SNARE 蛋白 SEC22B 在抗原交叉呈递中的作用的批判性分析。
DOI：
10.1016/j.celrep.2017.06.013
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发表时间：
2017-06-27
期刊：
影响因子：
8.8
通讯作者：
Reddy P
中科院分区：
文献类型：
--
作者：
Wu SJ;Niknafs YS;Kim SH;Oravecz-Wilson K;Zajac C;Toubai T;Sun Y;Prasad J;Peltier D;Fujiwara H;Hedig I;Mathewson ND;Khoriaty R;Ginsburg D;Reddy P
交叉呈递通过在MHC I上呈递细胞外抗原以激活CD 8 + T细胞介导的细胞毒性来启动针对肿瘤和病毒感染的免疫应答。在树突状细胞（DC）的体外研究建立了SNARE蛋白SEC 22 B作为交叉呈递的特异性调节剂。然而，SEC 22 B对交叉呈递的体内贡献尚未测试。为了解决这个问题，我们产生了DC特异性Sec 22 b敲除（CD 11 c-Cre Sec 22 bfl/fl）小鼠。与范例相反，SEC 22 B缺陷型DC在体内和体外均有效地交叉呈递。尽管体外shRNA介导的Sec 22 b沉默在骨髓来源的树突状细胞（BMDC）中减少了交叉呈递，但用相同的shRNA处理SEC 22 B缺陷的BMDC产生了类似的缺陷，表明Sec 22 b shRNA通过脱靶效应调节交叉呈递。SEC 22 b shRNA处理的SEC 22 B缺陷型BMDC的RNAseq显示转录组中的几个变化。我们的数据表明，与公认的模型相反，SEC 22 B不是交叉呈递所必需的，警告不要单独从敲除研究中推断表型。
Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8+ T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs) established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22bfl/fl) mice. Contrary to paradigm, SEC22B-deficient DCs efficiently cross-present both in vivo and in vitro. Though in vitro shRNA-mediated Sec22b silencing in bone marrow-derived dendritic cells (BMDCs) reduced cross-presentation, treatment of SEC22B-deficient BMDCs with the same shRNA produced a similar defect, suggesting the Sec22b shRNA modulates cross-presentation through off-target effects. RNAseq of Sec22b shRNA-treated SEC22B-deficient BMDCs demonstrated several changes in the transcriptome. Our data demonstrate that, contrary to the accepted model, that SEC22B is not necessary for cross-presentation, cautioning against extrapolating phenotypes from knockdown studies alone.
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