Metabolic Reprogramming in Allergen Immunotherapy

Allergies affect millions of people worldwide, causing symptoms ranging from sneezing and itchy eyes to life-threatening asthma attacks. While medications can relieve these symptoms, allergen immunotherapy is currently the only treatment that can actually cure allergies by gradually retraining the immune system to tolerate allergens like pollen or dust mites. However, despite its effectiveness, we still don`t fully understand how this therapy works at the molecular level, and why it doesn`t work equally well for everyone. This research project aims to uncover the metabolic mechanisms behind successful allergy treatment. Our immune system contains specialized cells called T cells that play opposing roles in allergies: Th2 cells promote allergic inflammation, while regulatory T cells (Tregs) help keep the immune response balanced. In allergic individuals, Th2 cells are overactive while Tregs are less effective. We believe these immune cells use energy and nutrients differently in allergic versus healthy people, and that successful immunotherapy changes how these cells metabolize fuel. To investigate this, we will develop innovative methods to measure key metabolites essential to central carbon metabolism (the cell`s core energy-producing pathways) and proteins from tiny samples of sorted T cells. Using these methods, we will analyze blood samples from allergic patients before, during, and after immunotherapy, comparing them with healthy individuals. By tracking how the metabolism of Th2 and Treg cells changes over the course of treatment, we aim to identify specific metabolic signatures that indicate successful therapy. This research could reveal why immunotherapy succeeds in some patients but not in others, potentially enabling doctors to predict treatment outcomes and personalize allergy care. The metabolic pathways we identify might also represent new targets for improving allergy treatment. Beyond allergies, the analytical methods developed in this project will be valuable for studying other diseases where immune cell metabolism plays a crucial role.