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.
Highlights
Allergic asthma is a type I hypersensitivity reaction of the upper and lower respiratory tract which affects more than 300 million people worldwide and represents one of the most common diseases
The present study focused on the role of b5i proteasome immunosubunit in experimental acute asthma
There is no information available on the role of this subunit in Th2 driven pathologies, while numerous reports have shown that b5i plays a role in Th1- and Th17- driven experimental inflammation such as DSS-induced colitis [14,15], Crohns disease and ulcerative colitis [12,23] and collagen-induced arthritis [16]
Summary
Allergic asthma is a type I hypersensitivity reaction of the upper and lower respiratory tract which affects more than 300 million people worldwide and represents one of the most common diseases. It is characterized by recurrent episodes of wheezing, breathlessness, chest tightness and coughing [1]. Processing and degradation of many proteins involved in signaling including NF-kB are mediated by proteasomes. The mammalian proteasome is a multicatalytic protease complex which is involved in protein degradation and processing of MHC I class antigens [6]. Immunoproteasomes show altered cleavage site specificity with improved MHC-I antigen presentation [9,10,11] and increased activation of NF-kB [12,13]
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