Researchers at La Jolla Institute for Immunology (LJI) study the root causes of food allergies with the goal of guiding novel therapeutics.
LJI Professor Toshiaki Kawakami, M.D., Ph.D., and his team study the activity of specific cells found in mucosal and connective tissues, called mast cells, in response to allergens from food. Mast cells can respond to allergens by triggering a range of symptoms and signs—from itching, wheezing, and sneezing to life-threatening anaphylaxis.
Dr. Kawakami and his colleagues have made progress in dissecting the complex network of signaling molecules involved in the early phase of mast cell activation. During allergic reactions, mast cells can be activated by an immune molecule called immunoglobulin E (IgE). For a long time, scientists believed that allergens ramp up levels of antibodies called immunoglobulin E (or IgE), which then bind to mast cells. They thought that when an allergen touches IgE, mast cells release histamine, the chemical that then drives inflammation and itching.
Dr. Kawakami’s work suggests that allergen levels are often too low to activate mast cells through this pathway. Instead, a 2017 study from his lab shows an important role for a small protein named histamine-releasing factor (HRF). This research confirms that HRF is triggered by allergens to bind to IgE. The two molecules then work together to activate mast cells and boost inflammation.
Dr. Kawakami’s lab is focused on developing potent HRF inhibitors to prevent anaphylaxis and is currently testing them in mouse models.