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

JCI Insight. 2017 Apr 6;2(7):e90721. doi: 10.1172/jci.insight.90721.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

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