CD 1d‐restricted invariant natural killer T (iNKT ) cells constitute a common glycolipid‐reactive innate‐like T‐cell subset with a broad impact on innate and adaptive immunity. While several microbial glycolipids are known to activate iNKT cells, the cellular mechanisms leading to endogenous CD 1d‐dependent glycolipid responses remain largely unclear. Here, we show that endoplasmic reticulum (ER ) stress in APC s is a potent inducer of CD 1d‐dependent iNKT cell autoreactivity. This pathway relies on the presence of two transducers of the unfolded protein response: inositol‐requiring enzyme‐1a (IRE 1α) and protein kinase R‐like ER kinase (PERK ). Surprisingly, the neutral but not the polar lipids generated within APC s undergoing ER stress are capable of activating iNKT cells. These data reveal that ER stress is an important mechanism to elicit endogenous CD 1d‐restricted iNKT cell responses through induction of distinct classes of neutral lipids.

中文翻译：

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抗原呈递细胞中的内质网应激通过内源性中性脂质促进NKT细胞活化。

CD 1d限制的不变自然杀伤T细胞（iNKT）构成常见的糖脂反应性先天样T细胞亚群，对先天和适应性免疫产生广泛影响。虽然已知有几种微生物糖脂可激活iNKT细胞，但导致内源性CD 1d依赖性糖脂反应的细胞机制仍不清楚。在这里，我们表明APC中的内质网（ER）应力是CD 1d依赖性iNKT细胞自身反应性的有效诱导剂。该途径依赖于未折叠蛋白反应的两种转化子的存在：需要肌醇的酶-1a（IRE1α）和蛋白激酶R样ER激酶（PERK）。令人惊讶的是，在经历内质网应激的APC中产生的中性而非极性脂质能够激活iNKT细胞。