Ablation of the Thiol Transferase Glutaredoxin-1 Augments Protein S-Glutathionylation and Modulates Type 2 Inflammatory Responses and IL-17 in a House Dust Mite Model of Allergic Airway Disease in Mice

S-glutathionylation has emerged as an oxidant-induced post-translational modification of protein cysteines that affects structure and function. The oxidoreductase glutaredoxin-1 (Glrx1), under physiological conditions, catalyzes deglutathionylation and restores the protein thiol group. The involvement of Grx1/S-glutathionylation in allergic inflammation induced by asthma-relevant allergens remains unknown. In the present study we examined the impact of genetic ablation of Glrx1 for the pathogenesis of house dust mite (HDM)-induced allergic airway disease in mice. Wild-type (WT) or Glrx1−/− mice in the BALB/c background were instilled intranasally with 50 μg of HDM 5 consecutive days for 3 weeks and killed 72 hours post final exposure. As expected, overall protein S-glutathionylation was increased in Glrx1−/− mice exposed to HDM as compared with WT animals. Total cells in the bronchoalveolar lavage fluid were similarly increased in WT and Glrx1−/− HDM-treated mice compared with phosphate-buffered saline–tr...