脂滴形成驱动ILC2介导的气道炎症

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本期文章:《免疫》:Online/在线发表

德国波恩大学Christoph Wilhelm及其团队探明了脂滴形成驱动气道炎症中的致病性2型先天性淋巴样细胞(ILC)。该研究于2020年4月7日发表于国际学术期刊《免疫》。

他们表示组织驻留类型2 ILC(ILC2s)在慢性激活后显示出独特的代谢特征。在过敏原引起的气道炎症中,ILC2s增加了其对外部脂质和葡萄糖的摄取。外部获得的脂肪酸瞬时存储在脂滴中,并转化为磷脂以促进ILC2的增殖。

该代谢程序由白介素33(IL-33)印记,并受基因Pparg和Dgat1调控,这两个基因均受葡萄糖可利用性和mTOR信号传导的控制。通过给小鼠提供生酮饮食来限制饮食中的葡萄糖,这会通过削弱脂肪酸代谢和脂滴的形成而大大消除ILC2介导的气道炎症。

总之,这些结果表明,致病性ILC2应答需要脂质代谢,并将生酮饮食确定为治疗气道炎症的有效干预策略。

据介绍,ILC在屏障免疫的控制和维持中起着重要作用。但是,ILC的慢性活化能够导致免疫介导的病理。

附:英文原文

Title: Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation

Author: Fotios Karagiannis, Schekufe Kharabi Masouleh, Klaus Wunderling, Jayagopi Surendar, Vanessa Schmitt, Alexander Kazakov, Marcel Michla, Michael Hlzel, Christoph Thiele, Christoph Wilhelm

Issue&Volume: 2020-04-07

Abstract: Innate lymphoid cells (ILCs) play an important role in the control and maintenanceof barrier immunity. However, chronic activation of ILCs results in immune-mediatedpathology. Here, we show that tissue-resident type 2 ILCs (ILC2s) display a distinctmetabolic signature upon chronic activation. In the context of allergen-driven airwayinflammation, ILC2s increase their uptake of both external lipids and glucose. Externallyacquired fatty acids are transiently stored in lipid droplets and converted into phospholipidsto 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. Restrictingdietary glucose by feeding mice a ketogenic diet largely ablated ILC2-mediated airwayinflammation by impairing fatty acid metabolism and the formation of lipid droplets.Together, these results reveal that pathogenic ILC2 responses require lipid metabolismand identify ketogenic diet as a potent intervention strategy to treat airway inflammation.

DOI: 10.1016/j.immuni.2020.03.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30116-3

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
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