Grant: Early Career Researcher Awards in Asthma

Allergic asthma is a chronic inflammatory disease driven by exaggerated immune responses to environmental allergens. In asthma, eosinophils are key effector cells that promote inflammation and tissue remodeling in the lung. Interestingly, recent findings suggest that the role of eosinophils expands from effector to memory cells. Innate immune memory, known as trained immunity, enhances cellular functions in secondary exposures. We propose to investigate the novel concept of eosinophil memory during allergic sensitization, and how targeting this memory can disrupt the allergic cycle. Our group is using a mouse model of intermittent low-dose house dust mite (HDM) exposure that mimics human asthma. In this model, eosinophils show strong inflammatory activation and respond more robustly upon re-exposure, consistent with features of trained immunity. We also demonstrate that prophylactic or therapeutic administration of the trained immunity inducer ß-glucan improves lung function, reduces eosinophil activation, and dampens airway inflammation. This project tests two aims: (1) to define the molecular and functional reprogramming of eosinophils in response to HDM exposure, and (2) to disrupt allergic inflammation by therapeutically reprogramming eosinophils using ß-glucan. We will assess eosinophil function after allergic sensitization through in vitro assays and epigenetic profiling, adoptive transfers in mice, and ultimately use parabiosis to determine the in vivo efficacy of ß-glucan-trained eosinophils. Ultimately, this work has the potential to uncover a new layer of immune regulation in asthma and to inform novel therapeutic strategies targeting the root of chronic allergic inflammation.