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

Mundt, Sarah; Engelhardt, Britta; Kirk, Christopher J; Groettrup, Marcus; Basler, Michael (2016). Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV-induced meningitis. European journal of immunology, 46(1), pp. 104-113. Wiley-VCH 10.1002/eji.201545578

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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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