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

Background: IL-13 receptor alpha 2 (IL-13R alpha 2) binds IL-13 with high affinity and modulates IL-13 responses. There are soluble and membrane forms of IL-13R alpha 2 generated by alternative splicing in mice, but human subjects express only the membrane form of IL-13R alpha 2 (memIL-13R alpha 2). Objective: We determined the role of memIL-13R alpha 2 in the development of allergic inflammation in mouse models of asthma. Methods: IL-13R alpha 2-deficient and memIL-13R alpha 2 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-13R alpha 2-deficient mice AHR and airway inflammation were attenuated compared with levels seen in wild-type mice after HDM challenge. Lung epithelial overexpression of memIL-13R alpha 2 in the IL-13R alpha 2-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-13R alpha 2-deficient mice, whereas lung epithelial overexpression of memIL-13R alpha 2 increased mucus production. Lung epithelial overexpression of memIL-13R alpha 2 had no effect on levels of the soluble form of IL-13R alpha 2 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-13R alpha 2 in the lung and suggest that memIL-13R alpha 2 might contribute to allergic inflammation.