A CD1d-dependent antagonist inhibits the activation of iNKT cells and prevents development of allergen-induced airway hyperreactivity (39.9)

Abstract

Abstract The prevalence of asthma continues to increase and its optimal treatment remains a significant therapeutic challenge. Recently, CD1d-restricted iNKT cells were found to play a critical role in the induction of airway hyperreactivity (AHR) in rodents and are associated with severe peristent asthma in humans. To test whether iNKT cell-targeted therapy could be used to treat allergen-induced airway hyperreactivity disease, mice sensitized with ovalbumin were treated with a CD1d-binding lipid antagonist, DPPE-PEG. A single dose of DPPE-PEG prevented the development of AHR and pulmonary infiltrates after ovalbumin challenge, but not the development of ovalbumin-specific Th2 responses. Because iNKT cells play a critical role in the development of AHR, the inhibition of iNKT activation by DPPE-PEG suggests a novel therapy for iNKT cell-mediated diseases such as asthma.