期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 316, 期 3, 页码 L407-L417出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00386.2018
关键词
airway hyperresponsiveness; allergic airway inflammation; asthma; NPY; Y-1 receptor
资金
- Novartis Pharma Research grant
- Daiichi-Sankyo Research Grant [A17-1612]
Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y-1 receptor. NPY modulates these cells via its Y-1 receptor; however, involvement of NPY in the pathophysiology of bronchial asthma, particularly airway hyperresponsiveness (AHR), has not been defined. NPY-deficient and wild-type mice were intranasally sensitized and challenged to house dust mite (HDM) extract, and airway responses were monitored. After sensitization and challenge, NPY-deficient mice showed significantly lower AHR than wild-type mice, and numbers of eosinophils and levels of type 2 cytokines [interleukin (IL)-4, IL-5, and IL-13] in bronchoalveolar lavage fluid were significantly lower. Type 2 cytokine production from splenic mononuclear cells of HDM-sensitized mice was also significantly lower in NPY-deficient mice. Flow cytometry analysis showed that the number of CD4 T cells and CD11c(+) antigen-presenting cells (APCs) was significantly lower in the lungs of NPY-deficient mice than in wildtype mice following sensitization and challenge. Significantly fewer CD11c(+) APCs phagocytosed HDM in the mediastinal lymph nodes of NPY-deficient mice than in those of wild-type mice. Treatment with BIBO-3304, a NPY receptor antagonist, significantly suppressed development of HDM-induced AHR and inflammation in wild-type mice. These data identify an important contribution of NPY to allergen-induced AHR and inflammation through accumulation of dendritic cells in the airway and promotion of the type 2 immune response. Thus, manipulating NPY represents a novel therapeutic target to control allergic airway responses.
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