2. Academic Validation
  3. Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation

Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation

  • J Exp Med. 2022 Mar 7;219(3):e20211001. doi: 10.1084/jem.20211001.
Gaoyu Liu 1 2 3 4,  Yingying Chen 2 3,  Ying Wang 2,  Xiaohui Deng 3,  Qiang Xiao 5,  Lijuan Zhang 2,  Haixu Xu 2,  Xu Han 2,  Aihua Lei 3,  Juan He 1,  Xing Li 6,  Yingjiao Cao 3,  Pan Zhou 2,  Chunhui He 7,  Peiqiong Wu 7,  Wenhui Jiang 7,  Meizheng Tan 8,  Chun Chen 4,  Quan Yang 9,  Liwei Lu 10,  Kai Deng 3,  Zhi Yao 2,  Jie Zhou 1 2
Affiliations

Affiliations

  • 1 Joint Program in Immunology, Department of Internal Medicine, Affiliated Guangzhou Women and Children's Medical Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 2 Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 3 Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 4 Division of Hematology/Oncology, Department of Pediatrics, Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
  • 5 Department of Clinical Laboratory, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
  • 6 Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 7 Department of Respiration, Guangzhou Women and Children's Medical Center, Guangzhou, China.
  • 8 Department of Child Health Care, Guangzhou Institute of Pediatrics, Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 9 Key Laboratory of Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 10 Department of Pathology and Shenzhen Institute of Research and Innovation, Shenzhen Hospital, University of Hong Kong, Hong Kong, China.
PMID: 35044462 DOI: 10.1084/jem.20211001
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.

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