Researchers at McMaster University have identified a new population of immune cells that may play a crucial role in the severity of asthma symptoms.

The study, published in Science Translational Medicine on Jan. 15, sheds light on the complex mechanisms behind severe asthma and opens new avenues for potential treatments.

Asthma is a chronic respiratory condition characterized by inflammation and narrowing of the airways, leading to difficulty breathing. Severe asthma, which affects up to 10 per cent of the general asthma population, is particularly challenging to treat because it is resistant to standard therapies.

“When you can’t breathe, nothing else matters,” says Roma Sehmi, senior and corresponding author of the paper and a professor in the department of Medicine.

“Our Hamilton-based group has been world leaders in evaluating the type of inflammation in the airways using methods developed to sample and examine sputum. We sought to better understand the mechanisms behind severe asthma so that we can better treat these patients.”

The research team recruited patients from St. Joseph’s Healthcare Hamilton and carried out experimental work at McMaster and the Firestone Institute for Respiratory Health (FIRH), a joint McMaster-St. Joseph’s research institute.

Researchers explored a unique group of immune cells in the airways of people with severe asthma. The cells, called c-kit+IL-17A+ ILC2s, can be likened to chameleons — they can change their characteristics and have traits of two different types of immune cells.

These “intermediate ILC2s” are linked to the presence of two types of cells  — eosinophils and neutrophils — that cause inflammation and make asthma worse, researchers found.

People with severe asthma have these chameleon-like ILC2s that show markers of another cell type, ILC3, which are associated with a high number of neutrophils in the airways — often seen in difficult-to-treat severe asthma, the study shows.

The study also found growth factors that encourage the formation of these intermediate ILC2s, suggesting that controlling their levels could prevent too many neutrophils from accumulating and worsening asthma symptoms.

The ability of ILC2s to change and take on features of ILC3s in the airways of asthma patients is a new discovery, offering insights into what drives severe asthma and pointing to potential new treatment targets.

“When asthma is associated with both eosinophils and neutrophils cells, individuals are generally less responsive to treatment with glucocorticosteroids — which are the mainstay of treatment for severe asthma,” said Parameswaran Nair, co-corresponding author of the paper and professor in the department of Medicine.

“The findings from this research pave the way for discovering new therapeutic targets for difficult-to-treat asthma.”

The study is the result of over a decade of collaborative research between Sehmi’s and Nair’s labs. The study involved contributions from several key researchers, including first author Xiaotian (Tim) Ju, who recently completed his PhD in Sehmi’s lab and is now a postdoctoral fellow at the National Institutes of Health in Bethesda, Maryland.

The study was funded in part by an educational grant from Hoffmann-La Roche and graduate scholarship awards from the MITACS accelerate program, Ontario Graduate Scholarship, and The Research Institute of St. Joe’s Hamilton.