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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)951-958.e6
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number4
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • IL-13
  • IL-13 receptor
  • airway hyperresponsiveness
  • airway inflammation
  • lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Chen, W., Sivaprasad, U., Gibson, A. M., Ericksen, M. B., Cunningham, C. M., Bass, S. A., Kinker, K. G., Finkelman, F. D., Wills-Karp, M., & Khurana Hershey, G. K. (2013). IL-13 receptor α2 contributes to development of experimental allergic asthma. Journal of Allergy and Clinical Immunology, 132(4), 951-958.e6. https://doi.org/10.1016/j.jaci.2013.04.016