Unique and Overlapping Gene Expression Patterns Driven by IL-4 and IL-13 in the Mouse Lung

J Allergy Clin Immunol. 2009 Apr;123(4):795-804.e8. doi: 10.1016/j.jaci.2009.01.003. Epub 2009 Feb 26.


Background: Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 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-gamma 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / etiology*
  • Female
  • Gene Expression Profiling*
  • Interleukin-13 / physiology*
  • Interleukin-4 / physiology*
  • Lung / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin-4 / physiology
  • Reverse Transcriptase Polymerase Chain Reaction


  • Allergens
  • Interleukin-13
  • Receptors, Interleukin-4
  • Interleukin-4