ALBERT

Description: Publication date: 20 November 2014 Source: Cell Reports, Volume 9, Issue 4 Author(s): Shogo Tanabe , Toshihide Yamashita Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, demyelination, and neurodegeneration in the CNS. Although it is important to prevent neurodegeneration for alleviating neurological disability, the molecular mechanism of neurodegeneration remains largely unknown. Here, we report that repulsive guidance molecule-a (RGMa), known to regulate axonal growth, is associated with neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. RGMa is highly expressed in interleukin-17-producing CD4 + T cells (Th17 cells). We induced EAE by adoptive transfer of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells and then inhibited RGMa with a neutralizing antibody. Inhibition of RGMa improves EAE scores and reduces neuronal degeneration without altering immune or glial responses. Th17 cells induce cultured cortical neuron death through RGMa-neogenin and Akt dephosphorylation. Our results demonstrate that RGMa is involved in Th17-cell-mediated neurodegeneration and that RGMa-specific antibody may have a therapeutic effect in MS. Graphical abstract Teaser The mechanism of neurodegeneration under inflammation in the CNS remains largely unknown. Tanabe and Yamashita demonstrate that RGMa is highly expressed in Th17 cells and induces dephosphorylation of Akt, leading to death of neurons. A neutralizing antibody to RGMa attenuates axonal degeneration and severity of Th17-cell-mediated autoimmune encephalomyelitis.