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.
Keywords: AHR; APTI; Airway hyperresponsiveness; Airway pressure-time index; BAL; BALF; Bronchoalveolar lavage; Bronchoalveolar lavage fluid; CLCA3; Chloride channel calcium activated 3; EMSA; Electrophoretic mobility shift assay; HDM; House dust mite; Human growth hormone; IL-13; IL-13 receptor; IL-13 receptor α1; IL-13 receptor α2; IL-13Rα1; IL-13Rα2; IL-4 receptor α; IL-4Rα; MCP; Membrane form of IL-13Rα2; Monocyte chemoattractant protein; PAS; Periodic acid–Schiff; Quantitative PCR; Rat Clara cell 10 kDa; STAT6; Signal transducer and activator of transcription 6; Soluble form of IL-13Rα2; airway hyperresponsiveness; airway inflammation; hGH; lung; memIL-13Rα2; qPCR; rCC10; sIL-13Rα2.
Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.