Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy.

Abstract

IL-33 is one of the critical cytokines that activates group 2 innate lymphoid cells (ILC2s) and mediates allergic reactions. Accumulating evidence suggests that IL-33 is also involved in the pathogenesis of several chronic inflammatory diseases. Previously, we generated an IL-5 reporter mouse and revealed that lung IL-5-producing ILC2s played essential roles in regulating eosinophil biology. In this study, we evaluated the consequences of IL-33 administration over a long period, and we observed significant expansion of ILC2s and eosinophils surrounding pulmonary arteries. Unexpectedly, pulmonary arteries showed severe occlusive hypertrophy that was ameliorated in IL-5- or eosinophil-deficient mice, but not in Rag2-deficient mice. This indicates that IL-5-producing ILC2s and eosinophils play pivotal roles in pulmonary arterial hypertrophy. Administration of a clinically used vasodilator was effective in reducing IL-33-induced hypertrophy and repressed the expansion of ILC2s and eosinophils. Taken together, these observations demonstrate a previously unrecognized mechanism in the development of pulmonary arterial hypertrophy and the causative roles of ILC2 in the process.

• Authors: Masashi Ikutani, Koichi Tsuneyama, Makoto Kawaguchi, Junya Fukuoka, Fujimi Kudo, Susumu Nakae, Makoto Arita, Yoshinori Nagai, Satoshi Takaki, Kiyoshi Takatsu
• Journal: JCI insight (JCI Insight) Vol. 2 Issue 7 Pg. e90721 (04 06 2017) ISSN: 2379-3708 [Electronic] United States
• PMID: 28405615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Interleukin-33
• Interleukin-5
• Rag2 protein, mouse

Topics

• Animals
• DNA-Binding Proteins (genetics)
• Eosinophils (immunology)
• Hypertrophy
• Immunity, Innate
• Interleukin-33 (pharmacology)
• Interleukin-5 (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pulmonary Artery (pathology)
• Th2 Cells (immunology)