Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV‐induced meningitis |
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| Authors: | Sarah Mundt Britta Engelhardt Christopher J. Kirk Marcus Groettrup Michael Basler |
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| Affiliation: | 1. Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany;2. Konstanz Research School Chemical Biology (KoRS‐CB), University of Konstanz, Konstanz, Germany;3. Theodor Kocher Institute, University of Bern, Bern, Switzerland;4. Onyx Pharmaceuticals, South San Francisco, CA, USA;5. Biotechnology Institute Thurgau at the University of Konstanz (BITg), Kreuzlingen, Switzerland |
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| Abstract: | In addition to antigen processing, immunoproteasomes were recently shown to exert functions influencing cytokine production by monocytes and T cells, T‐helper cell differentiation, and T‐cell survival. Moreover, selective inhibition of the immunoproteasome subunit LMP7 ameliorated symptoms of autoimmune diseases including CD4+ T‐cell mediated EAE. In this study, we show that LMP7 also plays a crucial role in the pathogenesis of lymphocytic choriomeningitis virus (LCMV)‐induced meningitis mediated by CTLs. Mice lacking functional LMP7 display delayed and reduced clinical signs of disease accompanied by a strongly decreased inflammatory infiltration into the brain. Interestingly, we found that selective inhibition and genetic deficiency of LMP7 affect the pathogenesis of LCMV‐induced meningitis in a distinct manner. Our findings support the important role of LMP7 in inflammatory disorders and suggest immunoproteasome inhibition as a novel strategy against inflammation‐induced neuropathology in the CNS. |
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| Keywords: | Cytotoxic T cells CNS inflammation Immunoproteasome LMP7 Lymphocytic choriomeningitis virus |
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