RAGE contributes to allergen driven severe neutrophilic airway inflammation via NLRP3 inflammasome activation in mice.

AA exposure induced robust neutrophil-dominant airway inflammation and increased BALF levels of Th1/Th17 cytokines in wild-type mice, which was significantly reduced in RAGE mice. Serum levels of IgE and IgG1 were increased similarly in both wild-type and RAGE mice. Pharmacological inhibition of NLRP3 blocked the effects of AA exposure and NLRP3 inflammasome activation was RAGE-dependent. Neutrophil extracellular traps were elevated in the BALF of wild-type but not RAGE mice and an atypical population of SiglecF+ neutrophils were identified in the BALF. Lastly, time-course studies found that RAGE expression promoted sustained neutrophil accumulation in the BALF of mice in response to AA.