Allergic airway responses to aeroallergens are differentially regulated by IL-13 receptor alpha 1 and dependent on IL-13:IL-4 ratios

Ref ID: 18430

Author:

Eric Cole, Dana Shik , Marc Rothenberg , Ariel Munitz

Author address:

The Tel Aviv
University, Clinical Microiology and Immunology, Tel Aviv, IL; Cincinnati
Children’s Hospital Medical Center, Division of Allergy and Immunology,
Cincinnati, OH, US

Full conference title:

European Respiratory Congress

Abstract:

Background: Studies using Il13ra1-/- mice demonstrated a critical role for IL-
13 Receptor (R) a1 in all allergen-induced airway responses except eosinophilia.
However, previous experiments were limited to mice sensitized with intraperitoneal
OVA and alum.
Aims: To define the role of IL-13Ra1 in allergic-airway inflammation in response
to aeroallergens and mucosal sensitization.
Methods: Wild type and Il13ra1-/- mice were challenged with Aspergilus fumigatus
(Asp) or housed dust mite (HDM) extracts (10 mg/mouse, 9 intranasal
challenges). Alternatively, Asp was absorbed to Alum (100 mg + 1 mg), mice
were sensitized (days 0 and 14, intraperitoneal) and challenged (days 24 and
27, intranasal). BALF was assessed for differential cell counts (Diff-Quick), Th2
cytokines and chemokines (ELISA, qPCR). Lung histology and resistance were
assessed by H&E, PAS stain and flexiVent respectively.
Results: Asp- and HDM-induced AHR and mucus production was IL-13Ra1-
dependent. Eosinophil recruitment to the lung as well as CCL17, CCL22 and
CCL24 production were IL-13Ra1 dependent following Asp-challenge but IL-
13Ra1-independent following HDM-challenge. Alum/Asp sensitized mice developed
IL-13Ra1-independent eosinophilia although all other asthma parameters
remained IL-13Ra1-dependent. Assessment of IL-4 and IL-13 mRNA levels
following Asp and HDM challenges revealed increased IL-13/IL-4 ratios in Aspchallenged
mice.
Conclusion: We highlight IL-13Ra1 as a key regulator of allergic lung responses
following aeroallergen sensitization and challenge. Nevertheless, outcomes of IL-
13Ra1-targeted asthma therapy may vary according to allergen-induced IL-4:IL-13
ratios.

Abstract Number: W3

Conference Year: 2011

Link to conference website: http://www.ers-education.org/ersMade/abstract_print_11/files/Abstract_book_2011.pdf

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