Identifying the role of RGMc in an animal model of Multiple Sclerosis

The Repulsive Guidance Molecule a (RGMa) has recently been implicated in the development of Multiple sclerosis (MS). We report for the first time that the third member of the RGM family, RGMc, is downregulated in the sera of mice induced with Experimental Autoimmune Encephalomyelitis (EAE), a well-characterized animal model of MS. Treatment with soluble RGMc (sRGMc) significantly delayed the onset of EAE and reduced the clinical severity of disease. Furthermore, RGMc knockout animals developed a stronger disease progression than wild-type controls. In vitro binding studies outlined a mechanism by which soluble RGMa and RGMc competed for interaction with their shared receptor, Neogenin. Finally, we demonstrated that administration of soluble RGMc halted leukocyte infiltration by interfering with the RGMa-mediated RhoA permeabilisation of the Blood-Brain Barrier (BBB). Overall, we show that RGMc treatment alleviated the clinical severity of EAE by enhancing BBB integrity and preventing leukocyte infiltration.M.Sc.2017-06-14 00:00:0