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January 16, 2025 — Researchers at McMaster University have made a groundbreaking discovery that may change the way we understand and treat severe asthma. A new study, published in Science Translational Medicine on January 15, 2025, uncovers a unique population of immune cells in the airways of people with severe asthma that may play a crucial role in the worsening of asthma symptoms.
Asthma, a chronic respiratory condition, is characterized by inflammation and narrowing of the airways, making it difficult to breathe. Severe asthma, affecting up to 10 percent of the general asthma population, is particularly difficult to treat, as it often does not respond to standard therapies.
Dr. Roma Sehmi, the senior author of the study and professor in the Department of Medicine at McMaster University, emphasized the significance of this discovery. “When you can’t breathe, nothing else matters,” she said. “Our goal is to understand the mechanisms behind severe asthma to improve treatments for these patients.”
The study, which involved patients from St. Joseph’s Healthcare Hamilton and research labs at McMaster University and the Firestone Institute for Respiratory Health, focuses on a new population of immune cells called c-kit+IL-17A+ ILC2s. These cells are described as “chameleon-like” because of their ability to change characteristics, adopting traits of two different types of immune cells. The researchers discovered that these intermediate ILC2s are linked to the presence of eosinophils and neutrophils—two types of immune cells that cause inflammation in the airways and contribute to the severity of asthma.
These intermediate ILC2s are particularly prevalent in patients with severe asthma, where they appear to transform into a form resembling ILC3 cells, which are associated with an increased presence of neutrophils in the airways. Neutrophils are commonly found in cases of difficult-to-treat asthma, and their accumulation is known to worsen symptoms.
In addition to identifying these chameleon-like immune cells, the research team also found growth factors that encourage the formation of intermediate ILC2s, which may help explain how an overproduction of neutrophils leads to asthma exacerbations. The study’s authors suggest that targeting these growth factors could be a potential strategy to control the levels of intermediate ILC2s and, in turn, prevent the accumulation of neutrophils that worsens asthma.
The findings offer new insights into the mechanisms driving severe asthma and suggest that by targeting the intermediate ILC2s, it may be possible to develop more effective treatments for patients who don’t respond well to traditional therapies such as glucocorticosteroids.
Parameswaran Nair, co-corresponding author of the study and professor at McMaster University, highlighted the therapeutic implications of the research. “When asthma is associated with both eosinophils and neutrophils, individuals are generally less responsive to glucocorticosteroids, which are the mainstay of treatment for severe asthma. Our findings open the door to discovering new therapeutic targets for these difficult-to-treat cases.”
This research is the result of over a decade of collaboration between Dr. Sehmi’s and Dr. Nair’s labs. Xiaotian (Tim) Ju, the first author of the study and a recent Ph.D. graduate from Dr. Sehmi’s lab, now continues his research as a postdoctoral fellow at the National Institutes of Health in Bethesda, Maryland.
The study’s results are poised to significantly impact the development of new treatments for severe asthma, offering hope to patients who suffer from this challenging and often debilitating condition.
For further details, the full study can be accessed at Science Translational Medicine: DOI: 10.1126/scitranslmed.ado6649.
