β5i Subunit Deficiency of the Immunoproteasome Leads to Reduced Th2 Response in OVA Induced Acute Asthma

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Abstract

The immunoproteasome subunit β5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function of β5i in Th2 dependent diseases remains enigmatic. To study the role of β5i in Th2-driven pathology, β5i knockout (KO) and control mice were tested in different models of experimental allergic asthma. β5i-deficient mice showed reduced OVA/Alum- and subcutaneous/OVA-induced acute asthma with decreased eosinophilia in the bronchoalveolar lavage (BAL), low OVA-specific IgG1 and reduced local and systemic Th2 cytokines. While Th2 cells in the lungs were reduced, Tregs and Th1 cells were not affected. Attenuated asthma in β5i KO mice could not be attributed to defects in OVA uptake or maturation of dendritic cells in the lung. Surprisingly, β5i deficient mice developed HDM asthma which was comparable to control mice. Here, we present novel evidence for the requirement of the β5i immunosubunit to generate a strong Th2 response during OVA- but not HDM-induced acute asthma. The unexpected role of β5i in OVA asthma remains to be clarified. © 2013 Volkov et al.

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Volkov, A., Hagner, S., Löser, S., Alnahas, S., Raifer, H., Hellhund, A., … Steinhoff, U. (2013). β5i Subunit Deficiency of the Immunoproteasome Leads to Reduced Th2 Response in OVA Induced Acute Asthma. PLoS ONE, 8(4). https://doi.org/10.1371/journal.pone.0060565

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