P2X3 Potentiates IgE Mediated Mast Cell Function

Abstract The rising incidence of allergic disease is a public health challenge needing novel interventions. Mast cell activation by IgE an established feature allergy, but fundamental aspects IgE-induced signaling remain unclear. Prior data from our lab testing the effects fluoxetine on IgE-driven mast function indicated role for purinergic receptor P2X3. P2X3 ATP-activated cationic channel most often associated with pain that expressed surface cells. cross-linkage elicits rapid release ATP cells, suggesting ATP-P2X3 may potentiate responses. We show diminishing pharmacologically and genetically reduces IgE-mediated cytokine production. knockout bone marrow-derived cells showed diminished capability to produce in vitro when stimulated cross-linkage. inhibitors BLU-5937 Gefapixant administered intraperitoneally suppressed levels measured plasma mice subjected cell-dependent passive systemic anaphylaxis model (PSA). Furthermore, knock-out reduced IL-6 compared wild-type PSA model. Interestingly, inhibition or deletion no effect degranulation did not reduce hypothermia during PSA. propose autocrine paracrine loop augments cell-mediated inflammation, thus offering potential new target treatment disease. RO1 AI164710-01, TL1 DK 132771-1