Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice

Autores
Funes, Samanta Celeste; Ríos, Mariana; Gómez Santander, Felipe; Fernández Fierro, Ayleen; Altamirano Lagos, María J.; Rivera Perez, Daniela; Pulgar Sepúlveda, Raul; Jara, Evelyn L.; Rebolledo Zelada, Diego; Villarroel, Alejandra; Roa, Juan C.; Mackern Oberti, Juan Pablo; Kalergis, Alexis M.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60–70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.
Fil: Funes, Samanta Celeste. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ríos, Mariana. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Gómez Santander, Felipe. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Fernández Fierro, Ayleen. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Fil: Altamirano Lagos, María J.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Rivera Perez, Daniela. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Pulgar Sepúlveda, Raul. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Fil: Jara, Evelyn L.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Rebolledo Zelada, Diego. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Villarroel, Alejandra. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Fil: Roa, Juan C.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Materia
AUTOIMMUNITY
HEME-OXYGENASE-1
SELF-TOLERANCE
SYSTEMIC LUPUS ERYTHEMATOSUS
TOLEROGENIC DENDRITIC CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/219136

id CONICETDig_9cf707d3c16976b6ac21cfe6e52273eb
oai_identifier_str oai:ri.conicet.gov.ar:11336/219136
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in miceFunes, Samanta CelesteRíos, MarianaGómez Santander, FelipeFernández Fierro, AyleenAltamirano Lagos, María J.Rivera Perez, DanielaPulgar Sepúlveda, RaulJara, Evelyn L.Rebolledo Zelada, DiegoVillarroel, AlejandraRoa, Juan C.Mackern Oberti, Juan PabloKalergis, Alexis M.AUTOIMMUNITYHEME-OXYGENASE-1SELF-TOLERANCESYSTEMIC LUPUS ERYTHEMATOSUSTOLEROGENIC DENDRITIC CELLShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60–70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.Fil: Funes, Samanta Celeste. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ríos, Mariana. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Gómez Santander, Felipe. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Fernández Fierro, Ayleen. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileFil: Altamirano Lagos, María J.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Rivera Perez, Daniela. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Pulgar Sepúlveda, Raul. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileFil: Jara, Evelyn L.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Rebolledo Zelada, Diego. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Villarroel, Alejandra. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileFil: Roa, Juan C.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; ChileWiley Blackwell Publishing, Inc2019-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/219136Funes, Samanta Celeste; Ríos, Mariana; Gómez Santander, Felipe; Fernández Fierro, Ayleen; Altamirano Lagos, María J.; et al.; Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice; Wiley Blackwell Publishing, Inc; Immunology; 158; 4; 9-2019; 322-3390019-2805CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/imm.13119info:eu-repo/semantics/altIdentifier/doi/10.1111/imm.13119info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:02:32Zoai:ri.conicet.gov.ar:11336/219136instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:02:32.615CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
title Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
spellingShingle Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
Funes, Samanta Celeste
AUTOIMMUNITY
HEME-OXYGENASE-1
SELF-TOLERANCE
SYSTEMIC LUPUS ERYTHEMATOSUS
TOLEROGENIC DENDRITIC CELLS
title_short Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
title_full Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
title_fullStr Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
title_full_unstemmed Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
title_sort Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice
dc.creator.none.fl_str_mv Funes, Samanta Celeste
Ríos, Mariana
Gómez Santander, Felipe
Fernández Fierro, Ayleen
Altamirano Lagos, María J.
Rivera Perez, Daniela
Pulgar Sepúlveda, Raul
Jara, Evelyn L.
Rebolledo Zelada, Diego
Villarroel, Alejandra
Roa, Juan C.
Mackern Oberti, Juan Pablo
Kalergis, Alexis M.
author Funes, Samanta Celeste
author_facet Funes, Samanta Celeste
Ríos, Mariana
Gómez Santander, Felipe
Fernández Fierro, Ayleen
Altamirano Lagos, María J.
Rivera Perez, Daniela
Pulgar Sepúlveda, Raul
Jara, Evelyn L.
Rebolledo Zelada, Diego
Villarroel, Alejandra
Roa, Juan C.
Mackern Oberti, Juan Pablo
Kalergis, Alexis M.
author_role author
author2 Ríos, Mariana
Gómez Santander, Felipe
Fernández Fierro, Ayleen
Altamirano Lagos, María J.
Rivera Perez, Daniela
Pulgar Sepúlveda, Raul
Jara, Evelyn L.
Rebolledo Zelada, Diego
Villarroel, Alejandra
Roa, Juan C.
Mackern Oberti, Juan Pablo
Kalergis, Alexis M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AUTOIMMUNITY
HEME-OXYGENASE-1
SELF-TOLERANCE
SYSTEMIC LUPUS ERYTHEMATOSUS
TOLEROGENIC DENDRITIC CELLS
topic AUTOIMMUNITY
HEME-OXYGENASE-1
SELF-TOLERANCE
SYSTEMIC LUPUS ERYTHEMATOSUS
TOLEROGENIC DENDRITIC CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60–70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.
Fil: Funes, Samanta Celeste. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ríos, Mariana. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Gómez Santander, Felipe. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Fernández Fierro, Ayleen. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Fil: Altamirano Lagos, María J.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Rivera Perez, Daniela. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Pulgar Sepúlveda, Raul. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Fil: Jara, Evelyn L.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Rebolledo Zelada, Diego. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Villarroel, Alejandra. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
Fil: Roa, Juan C.. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; Chile
Fil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; Chile. Universidad Católica de Chile; Chile
description Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60–70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.
publishDate 2019
dc.date.none.fl_str_mv 2019-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/219136
Funes, Samanta Celeste; Ríos, Mariana; Gómez Santander, Felipe; Fernández Fierro, Ayleen; Altamirano Lagos, María J.; et al.; Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice; Wiley Blackwell Publishing, Inc; Immunology; 158; 4; 9-2019; 322-339
0019-2805
CONICET Digital
CONICET
url http://hdl.handle.net/11336/219136
identifier_str_mv Funes, Samanta Celeste; Ríos, Mariana; Gómez Santander, Felipe; Fernández Fierro, Ayleen; Altamirano Lagos, María J.; et al.; Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice; Wiley Blackwell Publishing, Inc; Immunology; 158; 4; 9-2019; 322-339
0019-2805
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1111/imm.13119
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
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dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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