Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor

摘要: The role of the T helper (Th)17 pathway has been clearly demonstrated in onset and progression autoimmune diseases, where interleukin (IL)-23 is a key molecule maintaining response mediated by Th17 cells. As consequence, recent strategies based on blocking interaction between IL-23 its receptor (IL-23R), for example anti-p19 antibody tildrakizumab, have developed to regulate from initial stages disease. Here, soluble (s)IL-23R cDNA was cloned expression plasmids viral vectors. clinical efficacy sIL-23R evaluated myelin oligodendrocyte glycoprotein-induced experimental encephalomyelitis mice intravenously injected with single dose adeno-associated virus AAV8-sIL-23R Cytokine secretion determined multiplex assay, while histopathological analysis central nervous system performed study demyelination, inflammatory infiltration, microglia astroglia activation. We observed that administration vector 8 encoding associated significant disease improvement, including delay signs; slower progress disease; interference IL-23-mediated signal transducer activator transcription inhibiting 3 phosphorylation; reduced demyelination infiltration system; lower astrocyte Our results suggest use vectors carrying block IL-23/IL-23R may be new therapeutic strategy treatment multiple sclerosis.