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A1302 - Neuropeptide Y Is Required for the Development of Type-2 Responses and Allergen-Induced Airway Hyperresponsiveness and Inflammation
Author Block: N. Oda1, N. Miyahara2, A. Taniguchi1, D. Morichika1, S. Senoo1, U. Fujii1, M. Shibakura2, Y. Maeda1, K. Kiura3, A. Kanehiro1; 1Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan, 2Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, Japan, 3Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
BACKGROUND: Neuropeptide Y (NPY) is a neuropeptide widely expressed on the central nervous system. NPY is expressed on not only nervous system cells but also immune cells and respiratory epithelium; however, the involvement of NPY in the pathophysiology of bronchial asthma has not been defined. OBJECTIVE: To investigate the role of NPY in allergen-induced airway hyperresponsiveness and inflammation. METHODS AND RESULTS: NPY-deficient mice and wild-type mice were intranasally sensitized and challenged to house dust mite (HDM), and monitored airway responses. After sensitization and challenge, NPY-deficient mice showed significantly lower airway hyperresponsiveness compared with wild-type mice, and eosinophil numbers and levels of type 2 cytokines (IL-4, IL-5, and IL-13) in the bronchoalveolar lavage fluid were also significantly lower. Type 2 cytokine production from spleen mononuclear cells of HDM-sensitized mice was also significantly lower in NPY-deficient mice. Flow cytometric analysis of immune cells in the lungs showed that the numbers of CD4 T cells and CD11b positive dendritic cells were significantly lower in NPY-deficient mice compared to wild-type mice following sensitization and challenge. After fluorescently labeled HDM-challenge, the numbers of CD11c positive cells which phagocytosed fluorescently labeled HDM in the mediastinal lymph nodes of NPY-deficient mice were significantly lower than those of wild-type mice. Treatment with BIBO 3304, a NPY receptor antagonist, significantly suppressed the development of HDM-induced airway hyperresponsiveness and inflammation. CONCLUSION: These data identify the important contribution of NPY to allergen-induced airway hyperresponsiveness an inflammation through migration of dendritic cells to regional lymph nodes and promoting type-2 immune responses. Thus, manipulating NPY represents a novel therapeutic target in controlling allergic airway responses.