Y1 signalling has a critical role in allergic airway inflammation
Asthma affects 300 million people worldwide, yet the mechanism behind this pathology has only been partially elucidated. The documented connection between psychological stress and airway inflammation strongly suggests the involvement of the nervous system and its secreted mediators, including neuropeptides, on allergic respiratory disease. In this study, we show that neuropeptide Y (NPY), a prominent neurotransmitter, which release is strongly upregulated during stress, exacerbates allergic airway inflammation (AAI) in mice, via its Y1 receptor. Our data indicate that the development of AAI was associated with elevated NPY expression in the lung and that lack of NPY-mediated signalling in NPYKO mice or its Y1 receptor in Y1KO mice significantly improved AAI. In vivo, eosinophilia in the bronchoalveolar fluid as well as circulating immunoglobulin E in response to AAI, were significantly reduced in NPY- and Y1-deficient compared with wild-type mice. These changes correlated with a blunting of the Th2 immune profile that is characteristic for AAI, as shown by the decreased release of interleukin-5 during ex vivo re-stimulation of T cells isolated from the thoracic draining lymph nodes of NPY- or Y1-deficient mice subjected to AAI. Taken together this study demonstrates that signalling through Y1-receptors emerges as a critical pathway for the development of airway inflammation and as such potentially opens novel avenues for therapeutic intervention in asthma.Immunology and Cell Biology advance online publication, 8 March 2011; doi:10.1038/icb.2011.6.
|Authors||Macia, L.; Rao, P. T.; Wheway, J.; Sierro, F.; Mackay, F.; Herzog, H.|
|Responsible Garvan Author||Prof Herbert Herzog|
|Publisher Name||IMMUNOLOGY AND CELL BIOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21383768|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10968|