Requirement for neuropeptide Y in the development of type 2 responses and allergen-induced airway hyperresponsiveness and inflammation

Naohiro Oda, X. Nobuaki Miyahara, Akihiko Taniguchi, Daisuke Morichika, Satoru Senoo, Utako Fujii, Junko Itano, Yuka Gion, Katsuyuki Kiura, Arihiko Kanehiro, Yoshinobu Maeda

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Neuro-peptide 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 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.

Original languageEnglish
Pages (from-to)L407-L417
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number3
DOIs
Publication statusPublished - Mar 2019

Keywords

  • Airway hyperresponsiveness
  • Allergic airway inflammation
  • Asthma
  • NPY
  • Y receptor antagonist

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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