Exogenous interleukin-17a inhibits eosinophil differentiation and alleviates allergic airway inflammation

B. P. Tian, Wen Hua, Li Xia Xia, Yan Jin, Fen Lan, James J. Lee, Nancy A Lee, Wen Li, Song Min Ying, Zhi Hua Chen, Hua Hao Shen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

IL-17 is known to play important roles in immune and inflammatory disease, such as in asthma, but its functions in allergic airway inflammation are still controversial, and the molecular mechanisms mediating these functions remain unclear. Increased production of eosinophils in bone marrow and their emergence in the airway have been linked to the onset and progression of allergic asthma. In this study, we investigated the effects of exogenous IL-17 on allergic airway inflammation and explored the underlying molecular mechanisms through eosinophil generation. Exogenous IL-17 significantly attenuated the features of allergic inflammation induced by ovalbumin in mice. It inhibited eosinophil differentiation both in vivo and in vitro, accompanied by down-regulated expression of CC chemokine receptor 3, GATA binding protein 1 (GATA-1), and GATA binding protein 2 (GATA-2), as well as reduced formation of commonmyeloid progenitors and eosinophil progenitors, butwithout influencing eosinophil apoptosis. IL-17 also significantly decreased the number of eosinophils in IL-5-transgenic mice, although it notably increased the levels of IL-3, IL-5, and granulocyte/macrophage colony-stimulating factor. In addition, IL-17 had little effect on secretion of the inflammatory cytokines by eosinophils.Neutralization of endogenous IL-17 significantly augmented eosinophil recruitment in the airways. Together, these findings suggest that exogenous IL-17 protects against allergic airway inflammation, most likely through inhibition of the eosinophil differentiation in bone marrow.

Original languageEnglish (US)
Pages (from-to)459-470
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume52
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • Allergic airway inflammation
  • Differentiation
  • Eosinophil
  • IL-17A

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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