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 language | English |
|---|---|
| Pages (from-to) | e90721 |
| Journal | JCI insight |
| Volume | 2 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2017 Apr 6 |
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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 journal › Article
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TY - JOUR
T1 - Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy
AU - Ikutani, Masashi
AU - Tsuneyama, Koichi
AU - Kawaguchi, Makoto
AU - Fukuoka, Junya
AU - Kudo, Fujimi
AU - Nakae, Susumu
AU - Arita, Makoto
AU - Nagai, Yoshinori
AU - Takaki, Satoshi
AU - Takatsu, Kiyoshi
PY - 2017/4/6
Y1 - 2017/4/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85034832813&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034832813&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.90721
DO - 10.1172/jci.insight.90721
M3 - Article
C2 - 28405615
AN - SCOPUS:85034832813
VL - 2
SP - e90721
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 7
ER -