Mundt S Engelhardt B Kirk CJ Groettrup M Basler M 2016 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. application/pdf https://sonar.ch/global/documents/33717 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/eji.201545578 info:eu-repo/semantics/altIdentifier/pmid/26464284 info:eu-repo/semantics/openAccess 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 Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV-induced meningitis. http://purl.org/coar/resource_type/c_6501