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

Masashi Ikutani, Koichi Tsuneyama, Makoto Kawaguchi, Junya Fukuoka, Fujimi Kudo, Susumu Nakae, Makoto Arita, Yoshinori Nagai, Satoshi Takaki, Kiyoshi Takatsu

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e90721
JournalJCI Insight
Volume2
Issue number7
DOIs
Publication statusPublished - 2017 Apr 6

ASJC Scopus subject areas

  • Medicine(all)

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    Ikutani, M., Tsuneyama, K., Kawaguchi, M., Fukuoka, J., Kudo, F., Nakae, S., Arita, M., Nagai, Y., Takaki, S., & Takatsu, K. (2017). Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy. JCI Insight, 2(7), e90721. https://doi.org/10.1172/jci.insight.90721