The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells.
The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells.
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SNARE VAMP7调节了树突状细胞中白细胞介素12的胞外运输。
DOI：
10.1016/j.celrep.2016.02.055
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发表时间：
2016-03-22
期刊：
影响因子：
8.8
通讯作者：
Benvenuti F
中科院分区：
文献类型：
--
作者：
Chiaruttini G;Piperno GM;Jouve M;De Nardi F;Larghi P;Peden AA;Baj G;Müller S;Valitutti S;Galli T;Benvenuti F
白细胞介素-12 （IL-12）是树突状细胞在激活反应中产生的，是病原体根除和肿瘤排斥的核心。控制IL-12囊泡到细胞表面的空间分布和细胞内运输的运输途径尚不清楚。在这里，我们发现细胞内IL-12定位于由SNARE VAMP7标记的晚期内吞囊泡中。来自vamp7缺陷小鼠的树突状细胞（dc）在IL-12的多向释放中部分受损。当遇到抗原特异性T细胞时，含有IL-12的囊泡在免疫突触迅速重新分布并释放IL-12，这一过程完全依赖于VAMP7的表达。一致地，在VAMP7-null dc刺激的T细胞中，效应功能的获得减少。这些结果提供了对IL-12细胞内运输途径的见解，并表明vamp7介导的免疫突触释放IL-12是将先天信号传递给T细胞的一种机制。树突状细胞中IL-12的细胞内运输是由SNARE VAMP7介导的VAMP7是细胞外空间IL-12最佳分泌所必需的IL-12/VAMP7+囊泡聚集在免疫突触VAMP7控制T细胞中IL-12的突触释放和IFN-γ的产生有效启动T细胞需要抗原和可溶性细胞因子信号。Chiaruttini等人分析了树突状细胞中IL-12的细胞内转运途径，发现SNARE VAMP7是细胞因子释放和T细胞活化的关键调节因子。
Interleukin-12 (IL-12), produced by dendritic cells in response to activation, is central to pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution and intracellular transport of IL-12 vesicles to the cell surface are still unknown. Here, we show that intracellular IL-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs) from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Upon encounter with antigen-specific T cells, IL-12-containing vesicles rapidly redistribute at the immune synapse and release IL-12 in a process entirely dependent on VAMP7 expression. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. These results provide insights into IL-12 intracellular trafficking pathways and show that VAMP7-mediated release of IL-12 at the immune synapse is a mechanism to transmit innate signals to T cells. Intracellular trafficking of IL-12 in dendritic cells is mediated by the SNARE VAMP7 VAMP7 is required for optimal secretion of IL-12 in the extracellular space IL-12/VAMP7+ vesicles gather at the immune synapse VAMP7 controls synaptic release of IL-12 and IFN-γ production in T cells Efficient priming of T cells requires antigenic and soluble cytokine signals. Chiaruttini et al. analyze the intracellular trafficking pathway of IL-12 in dendritic cells and identify the SNARE VAMP7 as a key regulator of cytokine release and T cell activation.