Il-13 Receptor Alpha 1 Critically Regulates Lung Sensitization and Subsequent Inflammation (including Eosinophilia) in Response to Aspergillus Fumigatus

A. Munitz, E.T. Cole, M.M. Mingler, M.E. Rothenberg

Author address: 

Cincinati Children’s Hospital Medical Center, Cincinnati, OH.

Abstract: 

RATIONALE: We have previously shown that IL-13- and OVA-mediated lung effects are exclusively dependent on IL-13 receptor (R) α 1. While OVA-challenged Il13ra1-/- mice were entirely protected from airway hyperresponsiveness (AHR), fibrosis and mucus production, they still displayed substantial eosinophilia. Nevertheless, the role of IL-13Rα 1 in response to natural occurring allergen sensitization and challenge has not been assessed. METHODS: Experimental asthma was induced using the following protocols; a) Il13ra1-/- and wild type mice were chronically challenged (intranasally) with Aspergillus fumigatus (Asp) (three intranasal challenges/week for 3 weeks) or b) intraperitoneally sensitized with Alum/Asp (days 0,14) and subsequently intranasally challenged with Asp (days 24, 27). Forty-eight hours after the last challenge, the mice were sacrificed and lung tissue was excised for histology (H&E and PAS). Bronchoalveolar lavage fluid was obtained for differential cell counts and chemokine and TGF-β determination. Lung resistance and compliance AHR were measured using Flexivent. RESULTS: In response to chronic intranasal Asp-challenge, Il13ra1-/- mice were entirely protected from increased AHR, mucus production, chemokine and TGF-β induction as well as leukocyte (primarily eosinophil) recruitment. Interestingly, Il13ra1-/- mice that were intraperitoneally sensitized with Alum/Asp and subsequently intranasally challenged with Asp developed lung eosinophilia but were still protected from mucus induction, chemokine induction and TGF-β expression. Comparison of allergen-induced IgE production in the different experimental asthma protocols revealed IL-13Rα 1-dependent IgE production only in lung but not in systemic sensitization. CONCLUSIONS: These results establish a critical role for IL-13Rα 1 in mediating natural allergen-induced lung sensitization and imply a key role for IL-13Rα 1 in the local IgE response.
2010

abstract No: 

AB123

Full conference title: 

American Academy of Allergy Asthma & Immunology
    • AAAAI 2010 (66th)