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

• Published in: JCI insight 2017-04, Vol.2 (7), p.e90721-e90721
• Main Authors: Ikutani, Masashi, Tsuneyama, Koichi, Kawaguchi, Makoto, Fukuoka, Junya, Kudo, Fujimi, Nakae, Susumu, Arita, Makoto, Nagai, Yoshinori, Takaki, Satoshi, Takatsu, Kiyoshi
• Format: Article
• Language: English
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.90721

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.