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In neurodegeneration, grey matters: β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration

Experimental autoimmune encephalomyelitis (EAE) is quite possibly the most widely used animal model for multiple sclerosis (MS) and has shed light on several immunopathogenic processes that lead to this disease. On the other hand, grey matter degeneration -a crucial hallmark of the human MS- has always represented an elusive element in this model as EAE mice do not present grey matter damage, mostly due to the fact that the induction of the pathology is obtained mostly by triggering an immune reaction against myelin. Considering the emerging importance of this kind of lesion in MS, Dmitri Lodygin and colleagues sought to define a pathophisiologic process that underlied grey matter lesion.

Francesca Odoardi and Alexander Flugel’s groups discovered that a separated clonal set of T cells, specific for beta synuclein -a protein which is widely expressed in grey matter- is able to pass the blood brain barrier (BBB), cross the meninges and colonise grey matter, with their peak of infiltration corresponding to the clinical manifestations of neurodegeneration. Presence of beta-synuclein-specific T cells was also confirmed in peripheral blood of MS patients.

Source: Nature