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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6 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

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Interleukin-5
Eosinophils
Hypertrophy
Lung
Pulmonary Artery
Vasodilator Agents
Hypersensitivity
Chronic Disease
Lymphocytes
Cytokines
Interleukin-33

Cite this

Ikutani, M., Tsuneyama, K., Kawaguchi, M., Fukuoka, J., Kudo, F., Nakae, 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

Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy. / Ikutani, Masashi; Tsuneyama, Koichi; Kawaguchi, Makoto; Fukuoka, Junya; Kudo, Fujimi; Nakae, Susumu; Arita, Makoto; Nagai, Yoshinori; Takaki, Satoshi; Takatsu, Kiyoshi.

In: JCI insight, Vol. 2, No. 7, 06.04.2017, p. e90721.

Research output: Contribution to journalArticle

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, vol. 2, no. 7, pp. e90721. https://doi.org/10.1172/jci.insight.90721
Ikutani M, Tsuneyama K, Kawaguchi M, Fukuoka J, Kudo F, Nakae S et al. Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy. JCI insight. 2017 Apr 6;2(7):e90721. https://doi.org/10.1172/jci.insight.90721
Ikutani, Masashi ; Tsuneyama, Koichi ; Kawaguchi, Makoto ; Fukuoka, Junya ; Kudo, Fujimi ; Nakae, Susumu ; Arita, Makoto ; Nagai, Yoshinori ; Takaki, Satoshi ; Takatsu, Kiyoshi. / Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy. In: JCI insight. 2017 ; Vol. 2, No. 7. pp. e90721.
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