Signal Transduction Inhibition of APCs Diminishes Th17 and Th1 Responses in Experimental Autoimmune Encephalomyelitis

摘要: IL-17- and IFN-γ-secreting T cells play an important role in autoimmune responses multiple sclerosis the model system experimental encephalomyelitis (EAE). Dendritic (DCs) periphery microglia CNS are responsible for cytokine polarization expansion of this cell subset. Our results indicate that vivo administration a signal transduction inhibitor targets DCs to mice with EAE led decrease infiltration pathogenic Ag-specific cells. Since approach does not target directly, we assessed effects on APCs involved generating responses. sclerosis, both peripheral likely contribute disease, utilized bone marrow chimera distinguish between these two populations. These studies show primary but also modestly affected by CEP-701, as numbers activation states decreased after therapy. showed secretion TNF-α, IL-6, IL-23 well expression costimulatory molecules. We further determined levels phospho-Stat1, Stat3, Stat5, NF-κB, which signaling molecules have been implicated pathways, were decreased. Thus, use class inhibitors may represent novel method treat autoimmunity dampening autoreactive polarizing condition driven DCs.