Grant: Project Grant

This study focuses on specialized cells in the lung called Pulmonary Neuroendocrine Cells (PNEC). PNEC are found in the surface lining of the lung (epithelium) and are very rare (less than 1% of cells in the epithelium) but play an important role in detecting changes in the content of the air we breathe (oxygen levels, pollutants, bacteria), allowing the lungs to respond and maintain healthy function. PNEC are increased in number in asthmatics and recent studies, in mice, suggest that these cells play a key role in causing asthma and/or making asthma symptoms worse. However, very little is known about the function of human PNEC and how they contribute to asthma. We have established a novel method to culture human PNEC; allowing us to study the biology of a cell that is too rare to isolate from human lung tissue. Our own preliminary work shows that, when exposed to House Dust Mite (HDM), an inflammatory trigger in many asthmatics, PNEC start expressing Calcitonin Gene Related Peptide (CGRP), a neuropeptide known to enhance airway inflammation. In this study we will use our model of human PNEC to better understand how these cells respond to a range of common asthma triggers and how cells from asthmatics differ in their response to those from healthy individuals. We will also investigate how PNEC communicate with and alter the function of immune cells that play an important role in asthma. With successful completion of this project, we will gain an important understanding of PNEC and the role of this cell in Asthma. This knowledge may then be harnessed to develop entirely new approaches to asthma therapy with the possibility of reducing disease burden in those who do not respond to current treatments.