Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung

Christina C. Lewis, Bruce Aronow, John Hutton, Joanna Santeliz, Krista Dienger, Nancy Herman, Fred D. Finkelman, Marsha Wills-Karp

Research output: Contribution to journalArticle

Abstract

Background: Allergic asthma results from inappropriate TH2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives TH2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive. Objective: We sought to clarify the role or roles of IL-4 and IL-13 in asthma-pathogenesis. Methods: We used DNA Affymetrix microarrays to profile pulmonary gene expression in BALB/c mice inoculated intratracheally with ragweed pollen, house dust mite, IL-4, IL-13, or both cytokines. IL-13 dependence was confirmed by comparing pulmonary gene expression in house dust mite-inoculated wild-type and IL-13 knockout mice. Results: A signature gene expression profile consisting of 23 genes was commonly induced by means of inoculation with house dust mite, ragweed pollen, or IL-4 plus IL-13. Although rIL-4 and rIL-13 treatment induced an overlapping set of genes, IL-4 uniquely induced 21 genes, half of which were interferon response genes and half of which were genes important in immunoregulation. IL-13 uniquely induced 8 genes, most of which encode proteins produced by epithelial cells. Conclusions: IL-4 and IL-13 together account for most allergen-induced pulmonary genes. Selective IL-4 induction of IFN-γ response genes and other genes that might negatively regulate allergic inflammation could partially explain the greater importance of IL-13 in the effector phase of allergic airway disease.

Original languageEnglish (US)
Pages (from-to)795-804.e8
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • T2 cytokines
  • allergic asthma
  • microarrays
  • mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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