Researchers have made a significant advancement in asthma research by discovering a new type of immune cell that could be crucial in determining how severe asthma symptoms are.
At McMaster University, researchers have unveiled a significant finding related to asthma by identifying a novel type of immune cell that may be key to the severity of asthma symptoms.
The study, which was published in Science Translational Medicine on January 15, 2025, provides insights into the intricate mechanisms causing severe asthma and opens new pathways for potential treatments.
Asthma is a long-term respiratory condition marked by inflammation and constriction of the airways, resulting in breathing difficulties. Severe asthma, impacting around 10% of asthma patients, poses particular treatment challenges because it often does not respond to typical therapies.
“When you are unable to breathe, nothing else matters,” states Roma Sehmi, the senior author of the study and a professor in the Department of Medicine at McMaster University. “Our team in Hamilton is at the forefront of examining airway inflammation through innovative methods to sample and analyze sputum. We aimed to uncover the underlying mechanisms of severe asthma to improve treatment for these patients.”
The research team included patients from St. Joseph’s Healthcare Hamilton and conducted experiments in labs at McMaster University as well as the Firestone Institute for Respiratory Health (FIRH), a collaborative research institution involving both McMaster University and St. Joseph’s.
The researchers focused on a distinct group of immune cells found in the airways of individuals with severe asthma. Known as c-kit+IL-17A+ ILC2s, these cells can adapt, possessing features of two different immune cell types. The study revealed that these “intermediate ILC2s” are associated with the presence of two types of cells that contribute to inflammation and exacerbate asthma (eosinophils and neutrophils).
It was observed that individuals with severe asthma have these adaptable ILC2s displaying characteristics of another cell type, ILC3, which are linked to high levels of neutrophils in the airways — commonly seen in hard-to-treat severe asthma. Additionally, the research found growth factors that promote the development of these intermediate ILC2s, indicating that regulating their levels could help prevent excessive neutrophil buildup and alleviate asthma symptoms.
The finding that ILC2s can alter their characteristics to mimic ILC3s in asthma patients is a novel revelation. This insight enhances our understanding of what drives severe asthma and suggests potential new treatment targets. By elucidating the function of these intermediate ILC2s, the research team hopes to create improved therapies for severe asthma patients who do not respond effectively to current treatments.
“When both eosinophils and neutrophils are present in asthma cases, patients tend to be less responsive to glucocorticosteroids — the primary treatment for severe asthma. This research opens avenues for identifying new therapeutic targets for difficult-to-treat asthma,” noted Parameswaran Nair, co-corresponding author of the paper and a professor in the Department of Medicine at McMaster University.
The research is the culmination of more than ten years of collaboration between the laboratories of Sehmi and Nair. Key contributors to the study included first author Xiaotian (Tim) Ju, who recently finished his PhD in Sehmi’s lab and is now a postdoctoral fellow at the National Institutes of Health in Bethesda, Maryland.
This study received partial funding from an educational grant provided by Hoffmann-La Roche as well as graduate scholarship awards from the MITACS accelerate program, the Ontario Graduate Scholarship, and The Research Institute of St. Joe’s Hamilton.
