Administration of a COX-1-selective antagonist to mice completely prevented the generation of both PGD<sub>2</sub> and LTC<sub>4</sub> in a model of AERD in which MC activation is IL-33 driven.
Thus, CysLT<sub>2</sub>R signaling on platelets prominently utilizes RAGE/HMGB1 as a link to downstream type 2 respiratory immunopathology and IL-33-dependent mast cell activation typical of AERD.
Thus, IL-33 is a component of a cysLT-driven innate type 2 immune response that drives pathogenic MC activation and contributes substantially to AERD pathogenesis.