Web of Science: 4 citations, Scopus: 5 citations, Google Scholar: citations,
Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
Miralles, Marta (Universitat Autònoma de Barcelona. Institut de Neurociències)
Eixarch, Herena (Hospital universitari Vall Hebron. Institut de Recerca)
Tejero, Marcos (Universitat Autònoma de Barcelona. Institut de Neurociències)
Costa, Carme (Hospital universitari Vall Hebron. Institut de Recerca)
Hirota, Keiji (National Institute for Medical Research)
Castaño, A. Raul (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Puig, Meritxell (Universitat Autònoma de Barcelona. Institut de Neurociències)
Stockinger, Gitta (National Institute for Medical Research)
Montalban, Xavier (Hospital universitari Vall Hebron. Institut de Recerca)
Bosch, Assumpció (Universitat Autònoma de Barcelona. Institut de Neurociències)
Espejo, Carmen (Hospital universitari Vall Hebron. Institut de Recerca)
Chillon, Miguel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular
Universitat Autònoma de Barcelona. Departament de Biologia Celular, de Fisiologia i d'Immunologia

Date: 2017
Abstract: 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.
Abstract: The online version of this article (doi:10. 1007/s13311-017-0545-8) contains supplementary material, which is available to authorized users.
Note: Número d'acord de subvenció AGAUR/2014/SGR-1354
Note: Número d'acord de subvenció AGAUR/2014/SGR-1082
Note: Número d'acord de subvenció ISCIII/PI15-01270
Note: Número d'acord de subvenció MINECO/CP13/00028
Rights: 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. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Multiple sclerosis ; IL-23R ; Th17 ; EAE ; AAV vector
Published in: Neurotherapeutics, Vol. 14 (June 2017) , p. 1095-1106, ISSN 1878-7479

PMID: 28593439
DOI: 10.1007/s13311-017-0545-8


12 p, 4.5 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2018-02-08, last modified 2019-02-06



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