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

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-...

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Autores: Miralles, Marta, Eixarch, Herena|||0000-0001-7525-9533, Tejero Ambrosio, Marcos, Costa, Carme|||0000-0001-9577-3839, Hirota, Keiji, Castaño, Ángel Raúl|||0000-0003-2107-8862, Puig Ferrer, Meritxell, Stockinger, Gitta, Montalban, Xavier|||0000-0002-0098-9918, Bosch i Merino, Assumpció|||0000-0002-7205-2796, Espejo, Carmen|||0000-0001-9949-5901, Chillón Rodríguez, Miguel|||0000-0003-0840-2111
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186265
Acceso en línea:https://ddd.uab.cat/record/186265
https://dx.doi.org/urn:doi:10.1007/s13311-017-0545-8
Access Level:acceso abierto
Palabra clave:Multiple sclerosis
IL-23R
Th17
EAE
AAV vector
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spelling Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 ReceptorMiralles, MartaEixarch, Herena|||0000-0001-7525-9533Tejero Ambrosio, MarcosCosta, Carme|||0000-0001-9577-3839Hirota, KeijiCastaño, Ángel Raúl|||0000-0003-2107-8862Puig Ferrer, MeritxellStockinger, GittaMontalban, Xavier|||0000-0002-0098-9918Bosch i Merino, Assumpció|||0000-0002-7205-2796Espejo, Carmen|||0000-0001-9949-5901Chillón Rodríguez, Miguel|||0000-0003-0840-2111Multiple sclerosisIL-23RTh17EAEAAV vectorThe 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.The online version of this article (doi:10.1007/s13311-017-0545-8) contains supplementary material, which is available to authorized users.Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia MolecularUniversitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/186265https://dx.doi.org/urn:doi:10.1007/s13311-017-0545-8reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1354Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1082Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-01270Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CP13/00028open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1862652026-06-06T12:50:31Z
dc.title.none.fl_str_mv Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
title Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
spellingShingle Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
Miralles, Marta
Multiple sclerosis
IL-23R
Th17
EAE
AAV vector
title_short Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
title_full Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
title_fullStr Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
title_full_unstemmed Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
title_sort Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor
dc.creator.none.fl_str_mv Miralles, Marta
Eixarch, Herena|||0000-0001-7525-9533
Tejero Ambrosio, Marcos
Costa, Carme|||0000-0001-9577-3839
Hirota, Keiji
Castaño, Ángel Raúl|||0000-0003-2107-8862
Puig Ferrer, Meritxell
Stockinger, Gitta
Montalban, Xavier|||0000-0002-0098-9918
Bosch i Merino, Assumpció|||0000-0002-7205-2796
Espejo, Carmen|||0000-0001-9949-5901
Chillón Rodríguez, Miguel|||0000-0003-0840-2111
author Miralles, Marta
author_facet Miralles, Marta
Eixarch, Herena|||0000-0001-7525-9533
Tejero Ambrosio, Marcos
Costa, Carme|||0000-0001-9577-3839
Hirota, Keiji
Castaño, Ángel Raúl|||0000-0003-2107-8862
Puig Ferrer, Meritxell
Stockinger, Gitta
Montalban, Xavier|||0000-0002-0098-9918
Bosch i Merino, Assumpció|||0000-0002-7205-2796
Espejo, Carmen|||0000-0001-9949-5901
Chillón Rodríguez, Miguel|||0000-0003-0840-2111
author_role author
author2 Eixarch, Herena|||0000-0001-7525-9533
Tejero Ambrosio, Marcos
Costa, Carme|||0000-0001-9577-3839
Hirota, Keiji
Castaño, Ángel Raúl|||0000-0003-2107-8862
Puig Ferrer, Meritxell
Stockinger, Gitta
Montalban, Xavier|||0000-0002-0098-9918
Bosch i Merino, Assumpció|||0000-0002-7205-2796
Espejo, Carmen|||0000-0001-9949-5901
Chillón Rodríguez, Miguel|||0000-0003-0840-2111
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia
dc.subject.none.fl_str_mv Multiple sclerosis
IL-23R
Th17
EAE
AAV vector
topic Multiple sclerosis
IL-23R
Th17
EAE
AAV vector
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/186265
https://dx.doi.org/urn:doi:10.1007/s13311-017-0545-8
url https://ddd.uab.cat/record/186265
https://dx.doi.org/urn:doi:10.1007/s13311-017-0545-8
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1354
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1082
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-01270
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CP13/00028
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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