Research reveals that inhaling dust mites can trigger the onset of allergic asthma.

The results of a recent study published in Nature Immunology shed light on how seemingly harmless substances, such as dust mites, pet dander, and pollen, can evade the immune system and trigger an allergic reaction, ultimately paving the way for the discovery of new therapeutic approaches for the treatment and prevention of allergic asthma.

“We often think of the immune system as an army fighting against the “bad guys.” While this is true, most of the time our immune system is dealing not with pathogenic microorganisms, but with dust and pollen that we inhale, plants and animals we consume, and objects we touch in our environment. The key question that drives my research is how our immune system distinguishes when to respond to microorganisms versus other substances in the environment,” says Amanda C. Poholek, Ph.D., the senior author and director of the Sequencing Center at the University of Pittsburgh School of Medicine.

When the immune system performs this task correctly, it is referred to as immune tolerance. However, when tolerance is disrupted, typically harmless environmental allergens can activate type 2 helper T cells (Th2), which are a type of immune cell that causes inflammation in allergic asthma and other allergic diseases.

Allergic asthma is the most common form of asthma, characterized by symptoms such as coughing, chest tightness, shortness of breath, and wheezing. According to Amanda Poholek, the prevalence of this debilitating condition is rising worldwide, placing a significant burden on healthcare systems.

To better understand how allergens activate Th2 cells and lead to allergic asthma, Poholek and her team employed a mouse model of the disease induced by inhalation of house dust mites. This model provides a more accurate representation of how humans encounter allergens compared to studies using subcutaneous or systemic allergen injections.

Utilizing new tools to track Th2 cells and observe when they are activated and where they migrate, the researchers discovered that a specific molecular pathway involving a protein called BLIMP1 is necessary for the formation of Th2 cells in the lymph node in response to house dust mite inhalation. These cells then move to the lungs and induce disease.

They also found that the expression of BLIMP1 requires two signaling molecules, or cytokines, known as IL2 and IL10.

“IL10 is usually considered an anti-inflammatory cytokine that dampens immune responses, so we were quite surprised to find that it actually promotes inflammation,” says Poholek. “This finding opens up therapeutic possibilities targeting IL10 that have not previously been considered, especially for patients with a recent diagnosis.”

According to the researchers, most patients with allergic asthma are treated with steroids that alleviate symptoms but do not address the underlying cause of the disease. There is a significant need for new treatment methods that can intervene at early stages before allergic asthma causes long-term damage to the airways.

When the researchers mapped the activation sites of Th2 in the lymph node, they were also surprised to discover foci of IL2 activity.

“IL2 is a very prominent cytokine, so we expected it to be dispersed throughout the lymph node,” says Poholek. “Instead, we found that IL2 is localized to specific areas. Now we have a lot of work ahead to determine how these areas are formed and whether their destruction can disrupt the formation of Th2 cells, halting the development of allergic asthma.”

In collaboration with colleagues from the departments of Pulmonology, Allergy, Critical Care, and Sleep Medicine, Poholek also plans to study lung tissue samples to investigate whether IL2 and IL10 may also be important factors in the development of Th2 cells in patients with allergic asthma and explore potential avenues for developing new therapeutic strategies.