Top-level science through the eyes of an expert.

This episode of Genoskin’s webinar series is scheduled for:
November 6th, 2025
8 a.m. (PDT) | 11 a.m. (EDT) | 5 p.m. (CEST)

Mast cells have been recognized as the primary effector cells in anaphylaxis for over half a century, yet key questions remain. How do mast cells detect allergens and trigger a rapid, systemic response? And why are food-induced allergic reactions often especially severe?

In this talk, Dr. Abraham will present findings from his team’s recent studies using mouse models of IgE-mediated anaphylaxis. The team discovered that mast cells can rapidly detect blood-borne allergens with the help of perivascular dendritic cells. These dendritic cells extend dendrites into blood vessels to sample circulating allergens and then transfer them to neighboring mast cells via extracellular vesicles.

When mast cells throughout the body are simultaneously activated by allergens, they undergo widespread degranulation, releasing granules that interact with peripheral nerves. This interaction causes the nerves to send false heat signals to the central nervous system (CNS), which responds by inducing hypothermic shock—a hallmark of severe anaphylaxis. These findings reveal a previously unrecognized neuroimmune pathway in which mast cells engage the CNS to amplify the anaphylactic response.

The team also identified a critical role for inflammasome components NLRP3 and ASC in mast cell degranulation. In their absence, mast cells fail to degranulate. Following IgE-mediated activation, these components localize to granule membranes and facilitate granule mobilization to the cell surface, enabling extracellular release.

Interestingly, the team found that mast cells previously exposed to endotoxins, such as those in the gut, co-release large amounts of IL-1β upon degranulation. This leads to a more severe, often lethal, anaphylactic response in mice. These findings may help explain why food-induced anaphylaxis is particularly dangerous and suggest new therapeutic targets for intervention.

Together, these studies reveal how mast cell activation by allergens can result in rapid systemic and neural responses, offering new insights into the pathogenesis of anaphylaxis and potential avenues for therapeutic development.