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Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung
Christina C Lewis1, Bruce Aronow, John Hutton
1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA.
The Journal of Allergy and Clinical Immunology
|March 3, 2009
Summary
Interleukin-4 (IL-4) and Interleukin-13 (IL-13) play distinct roles in allergic asthma. IL-13 is crucial for airway hyperresponsiveness, while IL-4 influences T(H)2 induction and immunoregulation.
Area of Science:
- Immunology
- Respiratory Medicine
- Molecular Biology
Background:
- Allergic asthma involves T(H)2-mediated inflammation, with both IL-4 and IL-13 contributing to pathogenesis.
- IL-4 primarily drives T(H)2 induction, whereas IL-13 is essential for airway hyperresponsiveness and goblet cell hyperplasia.
- The distinct molecular mechanisms of IL-4 and IL-13 in allergic asthma remain unclear despite shared signaling pathways.
Purpose of the Study:
- To elucidate the specific roles of IL-4 and IL-13 in the pathogenesis of allergic asthma.
- To differentiate the contributions of IL-4 and IL-13 to distinct phases of allergic airway disease.
Main Methods:
- Pulmonary gene expression was profiled using DNA microarrays in mice exposed to allergens (ragweed, house dust mite) or cytokines (IL-4, IL-13).
- Gene expression was analyzed in wild-type and IL-13 knockout mice challenged with house dust mite to confirm IL-13 dependence.
- Specific gene signatures induced by each cytokine were identified.
Main Results:
- A common gene expression profile of 23 genes was induced by allergens and the combination of IL-4 plus IL-13.
- IL-4 uniquely induced 21 genes, including interferon response and immunoregulation genes.
- IL-13 uniquely induced 8 genes, predominantly encoding epithelial cell-produced proteins.
Conclusions:
- IL-4 and IL-13 collectively account for the majority of allergen-induced pulmonary genes.
- IL-4's induction of IFN-gamma response genes may explain IL-13's greater role in the effector phase of allergic airway disease.
- These findings highlight the differential functions of IL-4 and IL-13 in allergic asthma.
