The epigenetic drug Trichostatin A ameliorates experimental autoimmune encephalomyelitis via T cell tolerance induction and impaired influx of T cells into the spinal cord.

摘要: Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization myelin antigen-specific lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment NOD mice with histone deacetylase inhibitor, Trichostatin A affords robust peptide induced experimental autoimmune encephalomyelitis, mouse model Protection was accompanied by hyperacetylation, and reduced inflammation axonal damage in spinal cord. Drug diminished generation CD4+ memory cells tolerance recognizing immunizing peptide. During early immunization period, producing GM-CSF+IFN-γ, GM-CSF+IL-17A, as well those expressing both IL-17A+IFN-γ (double-producers) were detected secondary lymphoid organs followed appearance IFN-γ GM-CSF. On other hand, Th1 appear first cord IL-17A Treatment substantially frequencies all secreting various lymphokines periphery These data indicate epigenetic modifications hyperacetylation facilitates induction leading migration mitigation neuronal improved clinical outcome. results suggest modulation genome may similarly offer benefits patients via abrogating function encephalitogenic without exerting severe side effects associated used disease-modifying therapies.