Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against extracellular pathogens and tumors. This is achieved through a process known as cross-presentation (XP), and, despite its biological importance, the mechanism(s) driving XP remains unclear. Here, we show that a cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) is up-regulated in response to innate immune stimuli and is recruited to phagosomes. Association of APOL7C with phagosomes led to phagosomal rupture and escape of engulfed antigens to the cytosol, where they could be processed via the endogenous MHC class I antigen processing pathway. Accordingly, mice deficient in APOL7C did not efficiently prime CD8 + T cells in response to immunization with bead-bound and cell-associated antigens. Together, our data indicate the presence of dedicated apolipoproteins that mediate the delivery of phagocytosed proteins to the cytosol of activated cDCs to facilitate XP.

中文翻译：

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形成孔的载脂蛋白 APOL7C 驱动树突状细胞吞噬体破裂和抗原交叉呈递


传统的树突状细胞 （cDC） 产生针对细胞外病原体和肿瘤的保护性细胞毒性 T 淋巴细胞 （CTL） 反应。这是通过称为交叉呈递 （XP） 的过程实现的，尽管其生物学重要性，但驱动 XP 的机制仍不清楚。在这里，我们表明一种称为载脂蛋白 L 7C （APOL7C） 的 cDC 特异性成孔蛋白在先天免疫刺激下上调并被募集到吞噬体中。APOL7C 与吞噬体的结合导致吞噬体破裂和吞噬的抗原逃逸到胞质溶胶中，在那里它们可以通过内源性 MHC I 类抗原加工途径进行加工。因此，缺乏 APOL7C 的小鼠在用微珠结合抗原和细胞相关抗原免疫后不能有效地引发 CD8 + T 细胞。总之，我们的数据表明存在专用载脂蛋白，这些载脂蛋白介导吞噬蛋白递送到活化 cDC 的胞质溶胶以促进 XP。