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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Alum Compounds / adverse effects
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Animals
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Asthma / chemically induced
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Asthma / genetics*
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Asthma / immunology*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Dendritic Cells / immunology
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Disease Models, Animal
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Female
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Male
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Mice
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Mice, Knockout
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Ovalbumin / adverse effects
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Ovalbumin / immunology
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Phenotype
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Proteasome Endopeptidase Complex / deficiency*
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / immunology
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T-Lymphocytes, Regulatory / immunology
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Th2 Cells / immunology*
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Th2 Cells / metabolism*
Substances
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Alum Compounds
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ovalbumin-alum
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Ovalbumin
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LMP7 protein
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Proteasome Endopeptidase Complex
Grants and funding
The work was supported by the University of Giessen and Marburg Lung Center (UGMLC) and by the collaborative research grant (DFG) SFB/TR22. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.