A groundbreaking study from the University of Pittsburgh reveals how house dust mites trigger allergic asthma by activating specific immune cells, offering hope for new therapeutic interventions
New research from the University of Pittsburgh has elucidated the mechanism by which house dust mites, a prevalent allergen, trigger allergic asthma through immune system activation in mice. The study, recently published in Nature Immunology, provides vital insights into how seemingly harmless substances like dust mites, pet dander and pollen induce allergic reactions. This revelation promises to inform the development of new therapeutic strategies to manage and treat allergic asthma.
“We often think of the immune system as an army that fights the bad guys,” senior author Amanda C. Poholek, a director of the Health Sciences Sequencing Core and assistant professor in Pitt’s Department of Immunology at the School of Medicine, said in a news release. “And while that’s true, most of the time your immune system is not encountering pathogens but dealing with dust and pollen that you breathe in, plants and animals that you eat and things that you touch in the environment. A big question that motivates my research is: How does our immune system know to respond to pathogens and not to self and the environment?”
When functional, the immune system can tolerate harmless environmental substances — a state known as immune tolerance. However, when tolerance fails, benign allergens can activate T Helper 2 (Th2) cells, a type of immune cell that sparks inflammation in allergic asthma and other allergic conditions.
Poholek emphasized the rising global prevalence of allergic asthma, a condition characterized by symptoms like coughing, chest tightness, shortness of breath and wheezing, which poses a significant burden on healthcare systems.
The research team utilized a mouse model that mimics human exposure to allergens via inhalation of house dust mites, offering a more accurate representation compared to previous methods involving under-the-skin injections.
Leveraging advanced tools to track Th2 cells and monitor their activation, the researchers uncovered a critical molecular pathway involving the protein BLIMP1, vital for generating Th2 cells in the lymph node. These cells subsequently migrate to the lungs, exacerbating asthma symptoms.
The study further identified two pivotal cytokines, IL2 and IL10, necessary for BLIMP1 expression. Contrary to prior beliefs, IL10, typically known for its anti-inflammatory properties, was found to promote inflammation in this context.
“This finding opens that door to therapeutic options targeting IL10, which hadn’t previously been considered, particularly for newly diagnosed patients,” Poholek added.
The research also revealed unexpected hotspots of IL2 activity within lymph nodes.
“IL2 is a very prominent cytokine, so we expected that it would be dispersed throughout the lymph node,” added Poholek. “Instead, we discovered that IL2 was localized to certain regions. Now, we have a lot more work to figure out how these regions form and whether disrupting these regions could disrupt the formation of Th2 cells, halting allergic asthma.”
The collaboration continues with colleagues from Pitt’s Division of Pulmonology, Allergy, Critical Care and Sleep Medicine, investigating the role of IL2 and IL10 in human lung tissues to further explore potential new treatment avenues for allergic asthma.