| First Author | Oda N | Year | 2019 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 316 |
| Issue | 3 | Pages | L407-L417 |
| PubMed ID | 30604629 | Mgi Jnum | J:272749 |
| Mgi Id | MGI:6280178 | Doi | 10.1152/ajplung.00386.2018 |
| Citation | Oda N, et al. (2019) Requirement for neuropeptide Y in the development of type 2 responses and allergen-induced airway hyperresponsiveness and inflammation. Am J Physiol Lung Cell Mol Physiol 316(3):L407-L417 |
| abstractText | Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y1 receptor. NPY modulates these cells via its Y1 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 wild-type 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. |
