RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells.

RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells.
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RAB43促进了CD8α+树突状细胞与细胞相关抗原的交叉表现。

DOI:
10.1084/jem.20160597
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发表时间:
2016-12-12
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Murphy KM
Murphy KM
中科院分区:
其他
文献类型:
--
作者:
Kretzer NM;Theisen DJ;Tussiwand R;Briseño CG;Grajales-Reyes GE;Wu X;Durai V;Albring J;Bagadia P;Murphy TL;Murphy KM

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RAB 43是CD8 α + DC特有的囊泡转运蛋白,定位于高尔基体。Kretzer等人表明,RAB 43对于CD8 α + DC在体外和体内对细胞相关抗原的最佳交叉呈递是必需的,但对于体外单核细胞衍生的DC的交叉呈递是不必要的。在这项研究中,为了检查经典树突状细胞(DC; cDC)的交叉呈递,我们评估了RAB 43的作用,与其他DC亚群和免疫谱系相比,RAB 43是一种由Batf3依赖性CD8 α +和CD103+选择性表达的蛋白质。使用特异性单克隆抗体,我们将RAB 43表达定位于高尔基体和LAMP 1 −胞质囊泡。具有Rab43的种系或条件性缺失的小鼠是存活的和可育的,并且具有正常的cDC发育,但显示出细胞相关抗原的体内和体外交叉呈递的缺陷。这种缺陷对cDC是特异性的,因为Rab43缺陷型单核细胞衍生的DC在细胞相关抗原的交叉呈递中没有显示出缺陷。这些结果表明,RAB 43提供了一种特异性的活性,用于选择性地通过CD8 α + DC而不是其他抗原呈递细胞进行交叉呈递。
RAB43 is a vesicular transport protein unique to CD8α+ DCs that is localized to the Golgi. Kretzer et al. show that RAB43 is necessary for optimal cross-presentation of cell-associated antigens by CD8α+ DCs in vitro and in vivo but that it is dispensable for cross-presentation by in vitro monocyte-derived DCs. In this study, to examine cross-presentation by classical dendritic cells (DCs; cDCs), we evaluated the role of RAB43, a protein found to be selectively expressed by Batf3-dependent CD8α+ and CD103+ compared with other DC subsets and immune lineages. Using a specific monoclonal antibody, we localized RAB43 expression to the Golgi apparatus and LAMP1− cytoplasmic vesicles. Mice with germline or conditional deletion of Rab43 are viable and fertile and have normal development of cDCs but show a defect for in vivo and in vitro cross-presentation of cell-associated antigen. This defect is specific to cDCs, as Rab43-deficient monocyte-derived DCs showed no defect in cross-presentation of cell-associated antigen. These results suggest that RAB43 provides a specialized activity used in cross-presentation selectively by CD8α+ DCs but not other antigen-presenting cells.
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