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| Pàgina inicial > Articles > Articles publicats > Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor |
(Hospital Universitari Vall d'Hebron) (Hospital Universitari Vall d'Hebron) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Hospital Universitari Vall d'Hebron) (Universitat Autònoma de Barcelona. Institut de Neurociències) (Hospital Universitari Vall d'Hebron) (Universitat Autònoma de Barcelona. Institut de Neurociències)| Data: | 2017 |
| Resum: | The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors. The clinical efficacy of sIL-23R was evaluated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis mice intravenously injected with a single dose of adeno-associated virus AAV8- sIL-23R vectors. Cytokine secretion was determined by multiplexassay, while histopathological analysis of the central nervous system was performed to study demyelination, inflammatory infiltration, and microglia and astroglia activation. We observed that administration of adeno-associated vector 8 encoding sIL-23R was associated with a significant disease improvement,including delay in the onset of the clinical signs; slower progress of the disease;interference with IL-23- mediated signal transducer and activator of transcription response by inhibiting of signal transducer and activator of transcription 3 phosphorylation; reduced demyelination and infiltration in the central nervous system; and lower astrocyte and microglia activation. Our results suggest that the use of vectors carrying sIL-23R to block the IL-23/IL-23R interaction may be a new therapeutic strategy for the treatment of multiple sclerosis. |
| Resum: | The online version of this article (doi:10. 1007/s13311-017-0545-8) contains supplementary material, which is available to authorized users. |
| Ajuts: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1354 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1082 Instituto de Salud Carlos III PI15-01270 Ministerio de Economía y Competitividad CP13/00028 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Multiple sclerosis ; IL-23R ; Th17 ; EAE ; AAV vector |
| Publicat a: | Neurotherapeutics, Vol. 14 (June 2017) , p. 1095-1106, ISSN 1878-7479 |
