The Mast Cell-Neuronal Axis in Anaphylaxis

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2025-09-14

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2023

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Abstract

IgE-mediated anaphylaxis is a dangerous systemic reaction to allergens and affect up to 50 million people in the United States, with the number of cases increasing every year. This reaction occurs when allergens enter the bloodstream and are recognized by IgE-sensitized mast cells (MCs), which leads to massive release of MC granules systemically. Mediators released from these granules have historically been believed to cause a sudden drop in blood pressure and core body temperature by promoting vasodilation and vascular leakage. However, here, we present evidence that in mice, the nervous system, specifically the thermoregulatory neural circuit, also plays a role in the drop in body temperature during IgE-mediated anaphylaxis. This neural circuit is activated by granule-borne chymase from mast cells and is sensed and encoded as a "pseudo-heat" signal, which leads to the activation of the warm thermoregulatory neural network. This activation then rapidly reduces thermogenesis in brown adipose tissue, contributing to hypothermia. Compared to wild-type mice, mice lacking chymase or TRPV1 (a receptor on sensory neurons) had a lesser drop in body temperature during IgE-mediated anaphylaxis. Additionally, systemic activation of TRPV1+ sensory neurons is sufficient to induce anaphylactic-like responses. Therefore, mast cell mediators, especially chymase, promote IgE-mediated anaphylaxis not only through their effects on blood vessels but also via the TRPV1-thermoregulatory neural circuit axis.

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Bao, Chunjing (2023). The Mast Cell-Neuronal Axis in Anaphylaxis. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/29100.

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