Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Cambridge CB2 0SZ, UK.
Institute for Cardiovascular Prevention, Ludwig-Maximilians-University (LMU), 80336 Munich, Germany.
Nat Commun. 2017 Jun 7;8:15781. doi: 10.1038/ncomms15781.
Type-2 innate lymphoid cells (ILC2) are a prominent source of type II cytokines and are found constitutively at mucosal surfaces and in visceral adipose tissue. Despite their role in limiting obesity, how ILC2s respond to high fat feeding is poorly understood, and their direct influence on the development of atherosclerosis has not been explored. Here, we show that ILC2 are present in para-aortic adipose tissue and lymph nodes and display an inflammatory-like phenotype atypical of adipose resident ILC2. High fat feeding alters both the number of ILC2 and their type II cytokine production. Selective genetic ablation of ILC2 in Ldlr mice accelerates the development of atherosclerosis, which is prevented by reconstitution with wild type but not Il5 or Il13 ILC2. We conclude that ILC2 represent a major innate cell source of IL-5 and IL-13 required for mounting atheroprotective immunity, which can be altered by high fat diet.
2 型先天淋巴细胞 (ILC2) 是 II 型细胞因子的主要来源,在黏膜表面和内脏脂肪组织中持续存在。尽管它们在限制肥胖方面发挥作用,但人们对 ILC2 如何对高脂肪喂养做出反应知之甚少,它们对动脉粥样硬化发展的直接影响也尚未得到探索。在这里,我们表明 ILC2 存在于腹主动脉脂肪组织和淋巴结中,并表现出不同于脂肪组织固有 ILC2 的炎症样表型。高脂肪喂养改变了 ILC2 的数量及其 II 型细胞因子的产生。在 Ldlr 小鼠中选择性地遗传消融 ILC2 会加速动脉粥样硬化的发展,但用野生型而非 Il5 或 Il13 ILC2 重建可预防这种情况。我们得出结论,ILC2 是产生 IL-5 和 IL-13 的主要先天细胞来源,这些细胞对于产生抗动脉粥样硬化免疫至关重要,高脂肪饮食可以改变这些细胞。