Pittsburgh, PA – November 19, 2024 – A study from the University of Pittsburgh has unveiled how inhaled house dust mites, a prevalent trigger of allergic asthma, activate the immune system and contribute to the disease in mice. The findings, published in Nature Immunology, provide crucial insights into how harmless substances like dust mites, pet dander, and pollen can provoke allergic reactions, potentially leading to new therapeutic strategies for managing allergic asthma.
Dr. Amanda C. Poholek, the study’s senior author and an assistant professor in the Department of Immunology at Pitt’s School of Medicine, explained that while the immune system is often seen as a defense mechanism against pathogens, it also continuously interacts with benign environmental elements. “A significant question driving my research is: How does our immune system discern between harmful pathogens and harmless environmental substances?” she stated.
When the immune system functions effectively, it establishes a state known as immune tolerance. However, this tolerance can break down, allowing normally harmless allergens to activate T Helper 2 (Th2) cells, which are instrumental in driving inflammation associated with allergic asthma and other allergic conditions. Allergic asthma, characterized by symptoms such as coughing, chest tightness, shortness of breath, and wheezing, is the most common form of asthma and is increasingly prevalent worldwide, placing a substantial burden on healthcare systems.
To investigate the mechanisms by which allergens activate Th2 cells and lead to allergic asthma, Poholek and her team employed a mouse model that closely mimics human exposure to allergens through inhalation, as opposed to systemic injections. This model provides a more accurate representation of how humans encounter allergens.
Utilizing advanced tracking tools, the researchers discovered that the inhalation of house dust mites necessitates a specific molecular pathway involving the protein BLIMP1 for the generation of Th2 cells in the lymph nodes. These activated cells then migrate to the lungs, where they contribute to disease development. Interestingly, this pathway was not required when dust mites were injected, highlighting the differences in immune response based on the route of allergen exposure.
The study also identified two signaling molecules, or cytokines, IL2 and IL10, as essential for the expression of BLIMP1. “We were surprised to find that IL10, typically viewed as an anti-inflammatory cytokine that suppresses immune responses, actually promotes inflammation in this context,” Poholek noted. This revelation suggests new therapeutic possibilities targeting IL10, particularly for newly diagnosed patients.
Currently, most patients with allergic asthma are treated with steroids, which alleviate symptoms but do not address the underlying causes of the disease. Poholek emphasized the urgent need for innovative treatments that facilitate early intervention before allergic asthma inflicts lasting damage on the airways.
The researchers also mapped Th2 activation within the lymph nodes, discovering localized hotspots of IL2 activity, contrary to their expectations that IL2 would be evenly distributed. “This finding prompts further investigation into how these regions are formed and whether disrupting them could prevent the formation of Th2 cells, potentially halting allergic asthma,” Poholek explained.
In collaboration with colleagues from the Pitt Division of Pulmonology, Allergy, Critical Care, and Sleep Medicine, Poholek plans to examine lung tissue samples to determine if IL2 and IL10 are also significant drivers of Th2 cells in allergic asthma patients, paving the way for new therapeutic developments.
This research was supported by the National Institutes of Health, the American Lung Association Innovation Award, the Research Advisory Committee at UPMC Children’s Hospital of Pittsburgh, and the Clinical and Translational Science Institute Pilot Award.
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