Melatonin contributes to the seasonality of multiple sclerosis relapses

Autores
Farez, Mauricio; Mascanfroni, Ivan Darío; Mendez Huergo, Santiago Patricio; Yeste, Ada; Murugaiyan, Gopal; Garo, Lucien P.; Balbuena Aguirre, María E.; Patel, Bonny; Ysrraelit, María C.; Zhu, Chen; Kuchroo, Vjay K.; Rabinovich, Gabriel Adrian; Quintana, Francisco; Correale, Jorge
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.
Fil: Farez, Mauricio. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Fil: Mascanfroni, Ivan Darío. Harvard Medical School; Estados Unidos
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Yeste, Ada. Harvard Medical School; Estados Unidos
Fil: Murugaiyan, Gopal. Harvard Medical School; Estados Unidos
Fil: Garo, Lucien P.. Harvard Medical School; Estados Unidos
Fil: Balbuena Aguirre, María E.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Fil: Patel, Bonny. Harvard Medical School; Estados Unidos
Fil: Ysrraelit, María C.. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Fil: Zhu, Chen. Harvard Medical School; Estados Unidos
Fil: Kuchroo, Vjay K.. Harvard Medical School; Estados Unidos
Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Quintana, Francisco. Harvard Medical School; Estados Unidos
Fil: Correale, Jorge. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Materia
Melatonin
Multiple Sclerosis
Autoimmunity
Cell Differentiation
Encephalomyelitis Autoimmune Experimental
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7741
Acceder
id CONICETDig_d4cbded0ac9bd231c2f1403c4a92b673
oai_identifier_str oai:ri.conicet.gov.ar:11336/7741
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Melatonin contributes to the seasonality of multiple sclerosis relapsesFarez, MauricioMascanfroni, Ivan DaríoMendez Huergo, Santiago PatricioYeste, AdaMurugaiyan, GopalGaro, Lucien P.Balbuena Aguirre, María E.Patel, BonnyYsrraelit, María C.Zhu, ChenKuchroo, Vjay K.Rabinovich, Gabriel AdrianQuintana, FranciscoCorreale, JorgeMelatoninMultiple SclerosisAutoimmunityCell DifferentiationEncephalomyelitis Autoimmune Experimentalhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.Fil: Farez, Mauricio. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; ArgentinaFil: Mascanfroni, Ivan Darío. Harvard Medical School; Estados UnidosFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Yeste, Ada. Harvard Medical School; Estados UnidosFil: Murugaiyan, Gopal. Harvard Medical School; Estados UnidosFil: Garo, Lucien P.. Harvard Medical School; Estados UnidosFil: Balbuena Aguirre, María E.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; ArgentinaFil: Patel, Bonny. Harvard Medical School; Estados UnidosFil: Ysrraelit, María C.. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; ArgentinaFil: Zhu, Chen. Harvard Medical School; Estados UnidosFil: Kuchroo, Vjay K.. Harvard Medical School; Estados UnidosFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Quintana, Francisco. Harvard Medical School; Estados UnidosFil: Correale, Jorge. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; ArgentinaCell Press2015-09-10info: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/11336/7741Farez, Mauricio; Mascanfroni, Ivan Darío; Mendez Huergo, Santiago Patricio; Yeste, Ada; Murugaiyan, Gopal; et al.; Melatonin contributes to the seasonality of multiple sclerosis relapses; Cell Press; Cell; 162; 6; 10-9-2015; 1338-13520092-86741097-4172enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2015.08.025info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570563/info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/abstract/S0092-8674(15)01038-7info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0092867415010387info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:17Zoai:ri.conicet.gov.ar:11336/7741instacron: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:34982025-09-29 10:14:17.475CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Melatonin contributes to the seasonality of multiple sclerosis relapses
title Melatonin contributes to the seasonality of multiple sclerosis relapses
spellingShingle Melatonin contributes to the seasonality of multiple sclerosis relapses
Farez, Mauricio
Melatonin
Multiple Sclerosis
Autoimmunity
Cell Differentiation
Encephalomyelitis Autoimmune Experimental
title_short Melatonin contributes to the seasonality of multiple sclerosis relapses
title_full Melatonin contributes to the seasonality of multiple sclerosis relapses
title_fullStr Melatonin contributes to the seasonality of multiple sclerosis relapses
title_full_unstemmed Melatonin contributes to the seasonality of multiple sclerosis relapses
title_sort Melatonin contributes to the seasonality of multiple sclerosis relapses
dc.creator.none.fl_str_mv Farez, Mauricio
Mascanfroni, Ivan Darío
Mendez Huergo, Santiago Patricio
Yeste, Ada
Murugaiyan, Gopal
Garo, Lucien P.
Balbuena Aguirre, María E.
Patel, Bonny
Ysrraelit, María C.
Zhu, Chen
Kuchroo, Vjay K.
Rabinovich, Gabriel Adrian
Quintana, Francisco
Correale, Jorge
author Farez, Mauricio
author_facet Farez, Mauricio
Mascanfroni, Ivan Darío
Mendez Huergo, Santiago Patricio
Yeste, Ada
Murugaiyan, Gopal
Garo, Lucien P.
Balbuena Aguirre, María E.
Patel, Bonny
Ysrraelit, María C.
Zhu, Chen
Kuchroo, Vjay K.
Rabinovich, Gabriel Adrian
Quintana, Francisco
Correale, Jorge
author_role author
author2 Mascanfroni, Ivan Darío
Mendez Huergo, Santiago Patricio
Yeste, Ada
Murugaiyan, Gopal
Garo, Lucien P.
Balbuena Aguirre, María E.
Patel, Bonny
Ysrraelit, María C.
Zhu, Chen
Kuchroo, Vjay K.
Rabinovich, Gabriel Adrian
Quintana, Francisco
Correale, Jorge
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Melatonin
Multiple Sclerosis
Autoimmunity
Cell Differentiation
Encephalomyelitis Autoimmune Experimental
topic Melatonin
Multiple Sclerosis
Autoimmunity
Cell Differentiation
Encephalomyelitis Autoimmune Experimental
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.
Fil: Farez, Mauricio. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Fil: Mascanfroni, Ivan Darío. Harvard Medical School; Estados Unidos
Fil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Yeste, Ada. Harvard Medical School; Estados Unidos
Fil: Murugaiyan, Gopal. Harvard Medical School; Estados Unidos
Fil: Garo, Lucien P.. Harvard Medical School; Estados Unidos
Fil: Balbuena Aguirre, María E.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Fil: Patel, Bonny. Harvard Medical School; Estados Unidos
Fil: Ysrraelit, María C.. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
Fil: Zhu, Chen. Harvard Medical School; Estados Unidos
Fil: Kuchroo, Vjay K.. Harvard Medical School; Estados Unidos
Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Quintana, Francisco. Harvard Medical School; Estados Unidos
Fil: Correale, Jorge. Fundacion para la Lucha contra las Enfermedades Neurologicas Infancia. Instituto de Investigaciones Neurologicas "Raul Carrea"; Argentina
description Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.
publishDate 2015
dc.date.none.fl_str_mv 2015-09-10
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/11336/7741
Farez, Mauricio; Mascanfroni, Ivan Darío; Mendez Huergo, Santiago Patricio; Yeste, Ada; Murugaiyan, Gopal; et al.; Melatonin contributes to the seasonality of multiple sclerosis relapses; Cell Press; Cell; 162; 6; 10-9-2015; 1338-1352
0092-8674
1097-4172
url http://hdl.handle.net/11336/7741
identifier_str_mv Farez, Mauricio; Mascanfroni, Ivan Darío; Mendez Huergo, Santiago Patricio; Yeste, Ada; Murugaiyan, Gopal; et al.; Melatonin contributes to the seasonality of multiple sclerosis relapses; Cell Press; Cell; 162; 6; 10-9-2015; 1338-1352
0092-8674
1097-4172
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2015.08.025
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570563/
info:eu-repo/semantics/altIdentifier/url/http://www.cell.com/abstract/S0092-8674(15)01038-7
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0092867415010387
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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score 13.070432

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