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

• Published in: Journal of allergy and clinical immunology Vol. 132; no. 4; pp. 951 - 958.e6
• Main Authors: Chen, Weiguo, Sivaprasad, Umasundari, Gibson, Aaron M., Ericksen, Mark B., Cunningham, Christie M., Bass, Stacey A., Kinker, Kayla G., Finkelman, Fred D., Wills-Karp, Marsha, Khurana Hershey, Gurjit K.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2013; Elsevier
• Subjects: airway hyperresponsiveness; airway inflammation; Allergy and Immunology; alternative splicing; animal models; Animals; asthma; Asthma - complications; Asthma - immunology; Asthma - metabolism; Asthma - pathology; Biological and medical sciences; blood serum; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - metabolism; Bronchial Hyperreactivity - pathology; Bronchoalveolar Lavage Fluid; calcium channels; Cell Membrane - metabolism; chemokines; Chronic obstructive pulmonary disease, asthma; Disease Models, Animal; dust; dust mites; enzyme-linked immunosorbent assay; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gene overexpression; genetically modified organisms; histology; Humans; Hypersensitivity - complications; Hypersensitivity - immunology; Hypersensitivity - metabolism; Hypersensitivity - pathology; IL-13; IL-13 receptor; Immunopathology; inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; interleukin-13; Interleukin-13 Receptor alpha2 Subunit - genetics; Interleukin-13 Receptor alpha2 Subunit - immunology; Interleukin-13 Receptor alpha2 Subunit - metabolism; lung; Lung - immunology; Lung - pathology; lungs; Male; Medical sciences; Mice; mucus; Pneumology; polymerase chain reaction; Pyroglyphidae; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; signal transduction; transcription factors; Western blotting; airway inflammation; airway hyperresponsiveness; IL-13Rα1; IL-13Rα2; PAS; BALF; hGH; IL-13; AHR; BAL; lung; HDM; IL-13 receptor; rCC10; EMSA; sIL-13Rα2; APTI; qPCR; STAT6; MCP; memIL-13Rα2; CLCA3; IL-4Rα; Membrane form of IL-13Rα2; Soluble form of IL-13Rα2; Rat Clara cell 10 kDa; Signal transducer and activator of transcription 6; IL-4 receptor α; Bronchoalveolar lavage; Chloride channel calcium activated 3; Electrophoretic mobility shift assay; Periodic acid–Schiff; Airway pressure-time index; IL-13 receptor α1; IL-13 receptor α2; House dust mite; Quantitative PCR; Monocyte chemoattractant protein; Human growth hormone; Bronchoalveolar lavage fluid; Lung disease; Allergy; Immunopathology; Hyperreactivity; Respiratory disease; Lung; Cytokine; Inflammation; Interleukin 13; Experimental study; Respiratory system; Asthma; Respiratory tract; Immunology; Bronchus disease; Obstructive pulmonary disease; Biological receptor; Airway hyperresponsiveness
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.04.016

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). We determined the role of memIL-13Rα2 in the development of allergic inflammation in mouse models of asthma. 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. 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. These data collectively support a distinct role for memIL-13Rα2 in the lung and suggest that memIL-13Rα2 might contribute to allergic inflammation.