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. 2019 Mar 1;316(3):L407-L417. doi: 10.1152/ajplung.00386.2018. Epub 2019 Jan 3.


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.

Keywords: NPY; Y receptor antagonist; airway hyperresponsiveness; allergic airway inflammation; asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Eosinophils / immunology
  • Hypersensitivity / pathology
  • Inflammation / genetics
  • Inflammation / pathology*
  • Lung / pathology*
  • Mice, Transgenic
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism*
  • Respiratory Hypersensitivity / metabolism*
  • Respiratory Hypersensitivity / pathology


  • Cytokines
  • Neuropeptide Y