Group 2 innate lymphoid cells (ILC2s) represent the major player during hyperresponsive airway inflammation. Peroxisome proliferator-activated receptor-γ (PPARγ) was highly expressed on ILC2 and its potential role in asthma has been suggested. However, the detailed mechanism underlying the effects of PPARγ on ILC2-induced airway inflammation remains to be fully understood. Here we identified PPARγ as a positive regulator of lung ILC2. Expression of PPARγ on ILC2 was dramatically induced upon interleukin-33 (IL-33) challenge. Deficiency of PPARγ in hematopoietic system in mice (PPARγ^fl/fl Vav1^Cre) significantly impaired the function of ILC2 in lung, which led to apparent alleviation of airway inflammation in response to IL-33 or Papain challenge, when compared with those in PPARγ^fl/fl littermates control. Mechanistic studies identified IL-33 receptor ST2 as a transcriptional target of PPARγ. Overexpression of ST2 rescued the functional defects of ILC2 lacking PPARγ. Collectively, these results demonstrated PPARγ as an important regulator of ILC2 during allergic airway inflammation, which sheds new lights on the importance of PPARγ in asthma.

第 2 组先天性淋巴样细胞 (ILC2s) 是高反应性气道炎症过程中的主要参与者。过氧化物酶体增殖物激活受体-γ (PPARγ) 在 ILC2 上高表达，其在哮喘中的潜在作用已被提出。然而，PPARγ 对 ILC2 诱导的气道炎症影响的详细机制仍有待充分了解。在这里，我们将 PPARγ 鉴定为肺 ILC2 的正调节因子。PPARγ 在 ILC2 上的表达在白细胞介素 33 (IL-33) 攻击后被显着诱导。与 PPARγ 相比，小鼠造血系统中 PPARγ 的缺乏 (PPARγ ^fl/fl Vav1 ^Cre ) 显着损害了肺中 ILC2 的功能，导致对 IL-33 或木瓜蛋白酶攻击的气道炎症反应明显减轻^fl/fl同窝仔对照。机制研究将 IL-33 受体 ST2 确定为 PPARγ 的转录靶点。ST2 的过表达挽救了缺乏 PPARγ 的 ILC2 的功能缺陷。总的来说，这些结果表明 PPARγ 是过敏性气道炎症期间 ILC2 的重要调节剂，这为 PPARγ 在哮喘中的重要性提供了新的思路。