Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation
Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation
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DOI：
10.1016/j.immuni.2020.03.003
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发表时间：
2020-04-14
期刊：
影响因子：
32.4
通讯作者：
Wilhelm, Christoph
中科院分区：
文献类型：
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作者：
Karagiannis, Fotios;Masouleh, Schekufe Kharabi;Wilhelm, Christoph
先天淋巴样细胞（ILCs）在屏障免疫的控制和维持中起着重要作用。然而，ILCs的慢性激活导致免疫介导的病理。在这里，我们发现组织驻留的2型ILCs （ILC2s）在慢性激活时显示出独特的代谢特征。在过敏原驱动的气道炎症的背景下，ILC2s增加了对外部脂质和葡萄糖的摄取。外部获得的脂肪酸在脂滴中短暂储存并转化为磷脂，促进ILC2s的增殖。这种代谢程序由白细胞介素-33 （IL-33）印迹，并由Pparg和Dgat1基因调控，这两个基因都受葡萄糖可利用性和mTOR信号传导控制。通过给小鼠喂食生酮饮食来限制饮食中的葡萄糖，通过损害脂肪酸代谢和脂滴的形成，在很大程度上消融了ilc2介导的气道炎症。总之，这些结果表明致病性ILC2反应需要脂质代谢，并确定生酮饮食是治疗气道炎症的有效干预策略。
Innate lymphoid cells (ILCs) play an important role in the control and maintenance of barrier immunity. However, chronic activation of ILCs results in immune-mediated pathology. Here, we show that tissue-resident type 2 ILCs (ILC2s) display a distinct metabolic signature upon chronic activation. In the context of allergen-driven airway inflammation, ILC2s increase their uptake of both external lipids and glucose. Externally acquired fatty acids are transiently stored in lipid droplets and converted into phospholipids to promote the proliferation of ILC2s. This metabolic program is imprinted by interleukin-33 (IL-33) and regulated by the genes Pparg and Dgat1, which are both controlled by glucose availability and mTOR signaling. Restricting dietary glucose by feeding mice a ketogenic diet largely ablated ILC2-mediated airway inflammation by impairing fatty acid metabolism and the formation of lipid droplets. Together, these results reveal that pathogenic ILC2 responses require lipid metabolism and identify ketogenic diet as a potent intervention strategy to treat airway inflammation.