TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity.

ABSTRACT: Mast cells and basophils are main drivers of allergic reactions and anaphylaxis, for which prevalence is rapidly increasing. Activation of these cells leads to a tightly controlled release of inflammatory mediators stored in secretory granules. The release of these granules is dependent on intracellular calcium (Ca²⁺) signals. Ca²⁺ release from endolysosomal compartments is mediated via intracellular cation channels, such as two-pore channel (TPC) proteins. Here, we uncover a mechanism for how TPC1 regulates Ca²⁺ homeostasis and exocytosis in mast cells in vivo and ex vivo. Notably, in vivo TPC1 deficiency in mice leads to enhanced passive systemic anaphylaxis, reflected by increased drop in body temperature, most likely due to accelerated histamine-induced

SUBMITTER: Arlt E 

PROVIDER: S-EPMC7395440 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature