Ablation of Glutaredoxin-1 Modulates House Dust Mite-Induced Allergic Airways Disease in Mice

Sidra M. Hoffman, Xi Qian, James D. Nolin, David G. Chapman, Shi Biao Chia, Karolyn G. Lahue, Robert Schneider, Jennifer L. Ather, Matthew J. Randall, David H. McMillan, Jane T. Jones, Douglas J. Taatjes, Minara Aliyeva, Nirav Daphtary, Sarah Abdalla, Lennart K. A. Lundblad, Ye-Shih Ho, Vikas Anathy, Charles G. Irvin, Emiel F. M. WoutersNiki L. Reynaert, Anne E. Dixon, Albert van der Vliet, Matthew E. Poynter, Yvonne M. W. Janssen-Heininger*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)


Protein S-glutathionylation (PSSG) is an oxidant-induced post-translational modification of protein cysteines that impacts structure and function. The oxidoreductase glutaredoxin-1 (Glrx1) under physiological conditions catalyzes deglutathionylation and restores the protein thiol group. The involvement of Glrx1/PSSG in allergic inflammation induced by asthma-relevant allergens remains unknown. In the present study, we examined the impact of genetic ablation of Glrx1 in the pathogenesis of house dust mite (HDM)-induced allergic airways disease in mice. Wild-type (WT) or Glrx1(-/-) mice were instilled intranasally with HD Mon 5 consecutive days for 3 weeks. As expected, overall PSSG was increased in Glrx1(-/-) HDM mice as compared with WT animals. Total cells in bronchoalveolar lavage fluid were similarly increased in HDM-treated WT and Glrx1(-/-) mice. However, in response to HDM, mice lacking Glrx1 demonstrated significantly more neutrophils and macrophages but fewer eosinophils as compared with HDM-exposed WT mice. mRNA expression of the Th2-associated cytokines IL-13 and IL-6, as well as mucin-5AC (Muc5ac), was significantly attenuated in Glrx1(-/-) HDM-treated mice. Conversely, mRNA expression of IFN-gamma and IL-17A was increased in Glrx1(-/-) HDM mice compared with WT littermates. Restimulation of single-suspensions isolated from lungs or spleens with HDM resulted in enhanced IL-17A and decreased IL-5 production in cells derived from inflamed Glrx1(-/-) mice compared with WT animals. Finally, HDM-induced tissue damping and elastance were significantly attenuated in Glrx1(-/-) mice compared with WT littermates. These results demonstrate that the Glrx1-PSSG axis plays a pivotal role in HDM-induced allergic airways disease in association with enhanced type 2 inflammation and restriction of IFN-gamma and IL-17A.
Original languageEnglish
Pages (from-to)377-386
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number3
Publication statusPublished - 1 Sept 2016


  • asthma
  • protein S-glutathionylation
  • IL-17A
  • IFN-gamma;
  • neutrophils

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