Adenosine restrains ILC2-driven allergic airway inflammation via A2A receptor.

Abstract

Although group 2 Innate Lymphoid Cells (ILC2s) play important roles in driving the pathogenesis of allergic airway inflammation, the molecular mechanisms regulating ILC2 responses remain to be fully elucidated. Adenosine signaling is emerging as an important factor to limit excessive inflammation and tissue damage, its role in ILC2-driven airway inflammation remains to be understood. Here we identify adenosine as a negative regulator of ILC2s and allergic airway inflammation. Elevation of adenosine was observed in lungs after protease papain challenge. Adenosine receptor A2A was abundantly expressed in lung ILC2s. The adenosine analog NECA significantly suppress ILC2s responses and relieved airway inflammation induced by IL-33 or papain. Conversely, blockage of adenosine synthesis by CD73 inhibitor APCP or deficiency of A2A aggravated murine airway inflammation. Adoptive transfer of ILC2s into immunodeficiency NCG mice demonstrated that the regulation of ILC2 by adenosine was cell intrinsic. Mechanistic studies showed that the effects of adenosine on ILC2s were associated with changes in transcriptional profiling, and the elevation of intracellular cAMP and resulted NF-κB downregulation. These observations indicate that adenosine-A2A signaling is a negative regulator of ILC2s, which confers protection against airway inflammation and represents a novel therapeutic target for controlling asthma.

• Authors: Qiang Xiao, Xu Han, Gaoyu Liu, Dongmei Zhou, Lijuan Zhang, Juan He, Haixu Xu, Pan Zhou, Quan Yang, Jiangfan Chen, Jie Zhou, Guanmin Jiang, Zhi Yao
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 15 Issue 2 Pg. 338-350 (02 2022) ISSN: 1935-3456 [Electronic] United States
• PMID: 34921233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Society for Mucosal Immunology.

Chemical References

• Adora2a protein, mouse
• Interleukin-33
• Receptor, Adenosine A2A
• Adenosine

Topics

• Adenosine (metabolism)
• Animals
• Hypersensitivity (immunology)
• Immunity, Innate
• Inflammation (immunology)
• Interleukin-33 (immunology)
• Lung (immunology)
• Lymphocytes (immunology)
• Mice
• Receptor, Adenosine A2A (immunology)