title: Exogenous interleukin-17A inhibits eosinophil differentiation and alleviates allergic airway inflammation.
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 common myeloid progenitors and eosinophil progenitors, but without 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.
authors.affiliation: 1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Bao-ping
authors.initials: BP
authors.lastname: Tian
authors.forename: Wen
authors.initials: W
authors.lastname: Hua
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Xia
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Fen
authors.initials: F
authors.lastname: Lan
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Song-min
authors.initials: SM
authors.lastname: Ying
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Chen
authors.forename: Hua-hao
authors.initials: HH
authors.lastname: Shen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D005260:Female; D020381:Interleukin-17 / Q000494:pharmacology* / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D000893:Anti-Inflammatory Agents; D020381:Interleukin-17
keywords: IL-17A; allergic airway inflammation; differentiation; eosinophil