Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
STING activation in alveolar macrophages and group 2 innate lymphoid cells suppresses IL-33–driven type 2 immunopathology
Li She, … , Yong Liu, Xiao-Dong Li
Li She, … , Yong Liu, Xiao-Dong Li
Published January 5, 2021
Citation Information: JCI Insight. 2021;6(3):e143509. https://doi.org/10.1172/jci.insight.143509.
View: Text | PDF
Research Article Immunology Inflammation

STING activation in alveolar macrophages and group 2 innate lymphoid cells suppresses IL-33–driven type 2 immunopathology

  • Text
  • PDF
Abstract

2′3′-cGAMP is known as a nonclassical second messenger and small immune modulator that possesses potent antitumor and antiviral activities via inducing the stimulator of IFN genes–mediated (STING-mediated) signaling pathway. However, its function in regulating type 2 immune responses remains unknown. Therefore, we sought to determine a role of STING activation by 2′3′-cGAMP in type 2 inflammatory reactions in multiple mouse models of eosinophilic asthma. We discovered that 2′3′-cGAMP administration strongly attenuated type 2 lung immunopathology and airway hyperreactivity induced by IL-33 and a fungal allergen, Aspergillus flavus. Mechanistically, upon the respiratory delivery, 2′3′-cGAMP was mainly internalized by alveolar macrophages, in which it activated the STING/IFN regulatory factor 3/type I IFN signaling axis to induce the production of inhibitory factors containing IFN-α, which blocked the IL-33–mediated activation of group 2 innate lymphoid (ILC2) cells in vivo. We further demonstrated that 2′3′-cGAMP directly suppressed the proliferation and function of both human and mouse ILC2 cells in vitro. Taken together, our findings suggest that STING activation by 2′3′-cGAMP in alveolar macrophages and ILC2 cells can negatively regulate type 2 immune responses, implying that the respiratory delivery of 2′3′-cGAMP might be further developed as an alternative strategy for treating type 2 immunopathologic diseases such as eosinophilic asthma.

Authors

Li She, Gema D. Barrera, Liping Yan, Hamad H. Alanazi, Edward G. Brooks, Peter H. Dube, Yilun Sun, Hong Zan, Daniel P. Chupp, Nu Zhang, Xin Zhang, Yong Liu, Xiao-Dong Li

×

Full Text PDF | Download (4.52 MB)


Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts