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Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV-induced meningitis.

  • Mundt S Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
  • Engelhardt B Theodor Kocher Institute, University of Bern, Bern, Switzerland.
  • Kirk CJ Onyx Pharmaceuticals, South San Francisco, CA, USA.
  • Groettrup M Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
  • Basler M Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
  • 2015-10-15
Published in:
  • European journal of immunology. - 2016
CNS inflammation
Cytotoxic T cells
Immunoproteasome
LMP7
Lymphocytic choriomeningitis virus
Animals
Antigen Presentation
Arenaviridae Infections
Disease Models, Animal
Flow Cytometry
Lymphocyte Activation
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Mice
Mice, Inbred C57BL
Mice, Knockout
Proteasome Endopeptidase Complex
T-Lymphocytes, Cytotoxic
English 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.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/33717
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