Neurons promote encephalitogenic CD4⁺ lymphocyte infiltration in experimental autoimmune encephalomyelitis.

ABSTRACT: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, leading to demyelination and axonal degeneration. Neuronal excitotoxity mediated by Ca²⁺/calmodulin-dependent protein kinase IIα (CaMKIIα) results in neuronal damage in experimental autoimmune encephalitis (EAE), an animal model of MS. Here, we define a critical role of excitatory neurons in the pathogenesis of CD4⁺ lymphocyte accumulation in EAE. We silenced the activity of excitatory neurons in a mouse model of targeted EAE using inhibitory designer receptors exclusively activated by designer drugs (DREADD) under a CaMKIIα promoter. Neuronal silencing mitigated clinical disease scores in EAE, reduced the expression of c-fos, Tnfα, Ccl2, and Ccr2 mRNAs i

SUBMITTER: Nakazato Y 

PROVIDER: S-EPMC7192891 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature