Immunopathology Unit, Institute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
Life & Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
Immunity. 2020 Apr 14;52(4):620-634.e6. doi: 10.1016/j.immuni.2020.03.003. Epub 2020 Apr 7.
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.
先天淋巴细胞（ILCs）在控制和维持屏障免疫方面发挥着重要作用。然而，ILCs 的慢性激活会导致免疫介导的病理。在这里，我们表明，组织驻留的 2 型先天淋巴细胞（ILC2）在慢性激活时表现出独特的代谢特征。在过敏原驱动的气道炎症的情况下，ILC2 增加了对外源脂质和葡萄糖的摄取。外源性获得的脂肪酸被短暂地储存在脂滴中，并转化为磷脂以促进 ILC2 的增殖。这种代谢程序由白细胞介素 33（IL-33）印记，并由基因 Pparg 和 Dgat1 调节，这两个基因都受葡萄糖可用性和 mTOR 信号的控制。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，在很大程度上消除了 ILC2 介导的气道炎症。这些结果表明，致病性 ILC2 反应需要脂代谢，并确定生酮饮食是治疗气道炎症的有效干预策略。
