Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
Sterile activation of invariant natural killer T cells by ER-stressed antigen-presenting cells
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DOI：
10.1073/pnas.1910097116
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发表时间：
2019-11-19
影响因子：
11.1
通讯作者：
Cerundolo, Vincenzo
中科院分区：
文献类型：
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作者：
Bedard, Melissa;Shrestha, Dilip;Cerundolo, Vincenzo
不变NKT（iNKT）细胞具有独特的能力，在抗肿瘤免疫应答和其他形式的无菌和非无菌炎症期间形成免疫。最近的研究已经强调了各种类型的内源性和病原体衍生的脂质抗原，可以在无菌和非无菌条件下触发iNKT细胞活化。然而，在无菌性炎症中驱动自身脂质抗原呈递的背景和机制仍不清楚。在这里，我们报告说，内质网（ER）强调髓样细胞，通过蛋白激酶RNA样ER激酶（PERK）途径调节的信号事件，增加CD1d介导的免疫原性内源性脂质物质的介绍，这导致在增强iNKT细胞活化在体外和体内。此外，我们证明，肌动蛋白细胞骨架重组在ER应激的结果在细胞表面上的CD1d的分布改变，这有助于增强iNKT细胞活化。这些结果定义了一种以前未鉴定的机制，该机制在无菌炎症期间控制iNKT细胞活化。
Invariant NKT (iNKT) cells have the unique ability to shape immunity during antitumor immune responses and other forms of sterile and nonsterile inflammation. Recent studies have highlighted a variety of classes of endogenous and pathogen-derived lipid antigens that can trigger iNKT cell activation under sterile and nonsterile conditions. However, the context and mechanisms that drive the presentation of self-lipid antigens in sterile inflammation remain unclear. Here we report that endoplasmic reticulum (ER)-stressed myeloid cells, via signaling events modulated by the protein kinase RNA-like ER kinase (PERK) pathway, increase CD1d-mediated presentation of immunogenic endogenous lipid species, which results in enhanced iNKT cell activation both in vitro and in vivo. In addition, we demonstrate that actin cytoskeletal reorganization during ER stress results in an altered distribution of CD1d on the cell surface, which contributes to enhanced iNKT cell activation. These results define a previously unidentified mechanism that controls iNKT cell activation during sterile inflammation.