IL-13 receptor α2 contributes to development of experimental allergic asthma.

Abstract

BACKGROUND:

IL-13 receptor α2 (IL-13Rα2) binds IL-13 with high affinity and modulates IL-13 responses. There are soluble and membrane forms of IL-13Rα2 generated by alternative splicing in mice, but human subjects express only the membrane form of IL-13Rα2 (memIL-13Rα2).

OBJECTIVE:

We determined the role of memIL-13Rα2 in the development of allergic inflammation in mouse models of asthma.

METHODS:

IL-13Rα2-deficient and memIL-13Rα2 lung epithelium-specific transgenic mice were challenged with house dust mite (HDM). Airway hyperresponsiveness (AHR) and inflammation were assessed based on the airway pressure-time index, bronchoalveolar lavage (BAL) cell counts, and lung histology. Mucus production was determined by means of periodic acid-Schiff staining of lung sections, Western blot analysis of chloride channel calcium activated 3 (CLCA3) expression in lung homogenates, and ELISA of Muc5ac in BAL fluid. The expression of cytokines and chemokines was determined by using RT-quantitative PCR.

RESULTS:

In IL-13Rα2-deficient mice AHR and airway inflammation were attenuated compared with levels seen in wild-type mice after HDM challenge. Lung epithelial overexpression of memIL-13Rα2 in the IL-13Rα2-deficient mice reconstituted AHR and inflammation to levels similar to those observed in HDM-challenged wild-type mice. Mucus production was attenuated in lungs from HDM-treated IL-13Rα2-deficient mice, whereas lung epithelial overexpression of memIL-13Rα2 increased mucus production. Lung epithelial overexpression of memIL-13Rα2 had no effect on levels of the soluble form of IL-13Rα2 in serum or BAL fluid and did not affect IL-13-dependent signal transducer and activator of transcription 6 activation in the lungs.

CONCLUSION:

These data collectively support a distinct role for memIL-13Rα2 in the lung and suggest that memIL-13Rα2 might contribute to allergic inflammation.

• Authors: Weiguo Chen, Umasundari Sivaprasad, Aaron M Gibson, Mark B Ericksen, Christie M Cunningham, Stacey A Bass, Kayla G Kinker, Fred D Finkelman, Marsha Wills-Karp, Gurjit K Khurana Hershey
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 132 Issue 4 Pg. 951-8.e1-6 (Oct 2013) ISSN: 1097-6825 [Electronic] United States
• PMID: 23763980 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Interleukin-13 Receptor alpha2 Subunit

Topics

• Animals
• Asthma (complications, immunology, metabolism, pathology)
• Bronchial Hyperreactivity (immunology, metabolism, pathology)
• Bronchoalveolar Lavage Fluid
• Cell Membrane (metabolism)
• Disease Models, Animal
• Female
• Humans
• Hypersensitivity (complications, immunology, metabolism, pathology)
• Inflammation (immunology, metabolism, pathology)
• Interleukin-13 Receptor alpha2 Subunit (genetics, immunology, metabolism)
• Lung (immunology, pathology)
• Male
• Mice
• Pyroglyphidae