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.
Meanwhile, researchers in the laboratory of LJI Professor Bjoern Peters, Ph.D., are taking a closer look at pediatric cow’s milk allergy. This allergy is very common, but its origins are a mystery. Adding to the mystery is the fact that around 80 percent of children with a cow’s milk allergy see the allergy disappear by adulthood. With support from the Institute’s Tullie and Rickey Families SPARK Awards program, via the Rosemary Kraemer Raitt Foundation., Peters Lab member Sloan Lewis, Ph.D., is examining how immune cells drive this allergy.
In a recent study, Dr. Lewis investigated how T cells in blood samples from allergic children responded to proteins in cow’s milk, and she tracked down which proteins sent T cells into attack mode. Drs. Peters and Lewis then compared T cell responses from these patients to T cell responses from pediatric patients with other food allergies—but not milk allergy. This investigation revealed T cell characteristics only seen in kids with cow’s milk allergy—an immune signature that may prove useful in designing a future diagnostic. [Read the study]