Judith Coppinger
Associate Professor, RCSI
Cystic fibrosis (CF) is a progressive, genetic disease caused by mutations in cystic fibrosis transmembrane regulator (CFTR). Defective CFTR causes a salt/water imbalance, leading to a buildup of mucus in the lungs.
As part of a clinical/translational research programme at the Royal College of Surgeons in Ireland and the Children’s Health Ireland, Dr Judith Coppinger and her research team have been investigating new mechanisms of inflammatory cell communication in respiratory diseases such as CF and chronic obstructive pulmonary disorder (COPD).
Lung inflammation and neutrophil damage
Although very different causes, CF is a rare genetic disease, and COPD is caused primarily by smoking. Respiratory symptoms, such as mucus buildup and coughing, are common in both diseases. Both are characterised by inflammation in the lung airways and a high number of white blood cell cells called neutrophils, which help fight bacteria. Neutrophils are key to a healthy immune response. However, they behave abnormally in diseases such as CF and COPD, causing damage to the lungs.
Understanding how EVs recruit neutrophils
now helps us therapeutically target
them and reduce inflammation.
Targeting neutrophils with EVs
Our research group focuses on discovering new ways to target neutrophils and reduce lung inflammation using small particles called extracellular vesicles (EVs). These are small sacks of protein and RNA released by every cell containing information about that cell. When EVs come from diseased cells, we can gain important insights into that disease.
Our group has shown EVs are higher in number in lung samples from persons with CF and COPD undergoing exacerbation (worsening) of symptoms. We have also shown that EVs can attract neutrophils in the lungs. Understanding how EVs recruit neutrophils now helps us therapeutically target them and reduce inflammation.
Future therapeutic solutions
New CF therapies like Kaftrio have been crucial in targeting the CFTR defect in CF, but they do not fully reduce inflammation or reverse existing lung damage. Our research shows that Kaftrio can alter vesicles, suggesting that EVs could serve as markers of therapeutic response for patients on these treatments. With help from the Science Foundation of Ireland and CF Foundation, we investigate these EVs both as biomarkers of treatment and therapeutic targets to reduce neutrophil inflammation in CF and COPD.