A team of researchers from the United States has discovered a mechanism instrumental in causing allergic asthma that may offer an exciting new target for treating the condition.
Experts from the Indiana University School of Medicine Department of Microbiology and Immunology have comprehensively analysed allergic asthma, which is a seasonal or intermittent form of asthma. Researchers discovered a cytokine that could potentially mitigate symptoms of the condition. The team stated that their novel discovery might help to innovate new treatments for allergic asthma.
Ben Ulrich, PhD, the lead author of the study, commented: “Asthma has no cure, and current treatments primarily focus on resolving the symptoms. While spending time in the high-risk asthma clinic at Riley Hospital for Children, I observed many patients had a more intermittent disease course. We went into the lab and developed models to more accurately define allergic memory and recall response in the lung.”
What is allergic asthma?
Recent estimates demonstrate that around 235 million people have asthma globally, with about 8% of the US population currently affected by the condition. Moreover, of people with asthma, nearly half of adults and 90% of children are classified as having allergic asthma.
Allergic asthma occurs when an individual inhales certain allergens, resulting in symptoms such as wheezing, coughing, and in serious cases, asthmatic exacerbation resulting in hospitalisation. These symptoms stem from inflammation, airway constriction, and mucus production.
When people with allergic asthma are exposed to seasonal allergens, which includes exposure to fungi, pollens, or other allergens that only arise at certain times of the year, antigen-presenting cells activate CD4 positive T-cells to secrete cytokines, which initiates the inflammatory process.
Targeting cytokines
For their investigation, the team analysed one particular cytokine – called interleukin 9 (IL-9) – to observe how it affects allergic memory responses. The researchers discovered a unique population of memory CD4 T-cells that generated IL-9, in addition to IL-5 and IL-13. These cells secreted IL-9 in an antigen-specific manner.
Furthermore, these cells expressed an IL-33 receptor called ST2 and amplified IL-9 production in the presence of IL-33 in an allergen-specific manner. The team found that blocking IL-9 resulted in a reduction in the expression of a range of genes that are associated with mucus production in the epithelial cells. Additionally, obstructing IL-9 resulted in a decrease in CD4 T-cells and B-cells and modified the expression of activation markers on microphages.
Mark Kaplan, PhD, chair of the IU School of Medicine Department of Microbiology and Immunology, and senior author of the study, said: “Asthma exists in multiple forms and seasonal or intermittent asthma can be very different from other forms because of chronic exposure to allergens. This study demonstrates targeting IL-9 in the lungs during seasonal allergies could help with lung inflammation. By focusing on a population of memory cells that mediate the allergic recall responses of the lungs, we could develop new targets for treatments.”
Other major collaborators on the project included Rakshin Kharwadkar, PhD, Michelle Chu, and Abigail Pajulas. Other faculty authors from IU School of Medicine include Amelia Linnemann, PhD, Matthew Turner, PhD, MD, and Yunlong Liu, PhD. Additional collaborators include investigators at the University of Virginia, Yale University, Mayo Clinic, and Universidad Nacional Autónoma de México.
