Type 2 innate lymphoid cells (ILC2s) play a critical role early in the response to infection by helminths and in the development of allergic reactions. ILC2s are also involved in the physiologic regulation of adipose tissue and its metabolic response to cold shock. We find that the metabolic sensor peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ILC2s of the lung and adipose tissue and increases responsiveness to IL-33. In turn, activation of ILC2 by IL-33 leads to increased expression of PPARγ, a prerequisite for proliferation and expression of the effector cytokines IL-5 and IL-13. In contrast, pharmacological inhibition of PPARγ leads to decreased expression of CD36 and fatty acid uptake, a necessary source of energy for ILC2s and of potential ligands for PPARγ. As a consequence, treatment of mice with a PPARγ antagonist reduces the severity of an ILC2-dependent acute airway inflammation. Together, our results demonstrate the critical role of the metabolic sensor PPARγ for the functions of ILC2s.

2 型先天性淋巴样细胞 (ILC2s) 在早期对蠕虫感染的反应和过敏反应的发展中起着关键作用。ILC2 还参与脂肪组织的生理调节及其对冷休克的代谢反应。我们发现代谢传感器过氧化物酶体增殖物激活受体 γ (PPARγ) 在肺和脂肪组织的 ILC2 中高表达，并增加对 IL-33 的反应性。反过来，IL-33 激活 ILC2 会导致 PPARγ 表达增加，这是效应细胞因子 IL-5 和 IL-13 增殖和表达的先决条件。相反，PPARγ 的药理学抑制导致 CD36 表达和脂肪酸摄取减少，这是 ILC2 和 PPARγ 潜在配体的必需能量来源。作为结果，用 PPARγ 拮抗剂治疗小鼠可降低 ILC2 依赖性急性气道炎症的严重程度。总之，我们的结果证明了代谢传感器 PPARγ 对 ILC2 功能的关键作用。