Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation
Gaoyu Liu, Yingying Chen, Ying Wang, Xiaohui Deng, Qiang Xiao, Lijuan Zhang, Haixu Xu, X D Han, Aihua Lei, Juan He, Xing Li, Yingjiao Cao, Pan Zhou, Chun-Hui He, Peiqiong Wu, Wenhui Jiang, Meizheng Tan, Chun Chen, Quan Yang, Liwei Lu, Kai Deng, Zhi Yao, Jie Zhou
Abstract
Group 2 innate lymphoid cells (ILC2s) have emerged as critical mediators in driving allergic airway inflammation. Here, we identified angiotensin (Ang) II as a positive regulator of ILC2s. ILC2s expressed higher levels of the Ang II receptor AT1a, and colocalized with lung epithelial cells expressing angiotensinogen. Administration of Ang II significantly enhanced ILC2 responses both in vivo and in vitro, which were almost completely abrogated in AT1a-deficient mice. Deletion of AT1a or pharmacological inhibition of the Ang II-AT1 axis resulted in a remarkable remission of airway inflammation. The regulation of ILC2s by Ang II was cell intrinsic and dependent on interleukin (IL)-33, and was associated with marked changes in transcriptional profiling and up-regulation of ERK1/2 phosphorylation. Furthermore, higher levels of plasma Ang II correlated positively with the abundance of circulating ILC2s as well as disease severity in asthmatic patients. These observations reveal a critical role for Ang II in regulating ILC2 responses and airway inflammation.