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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/7741
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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 Técnicas2025-09-03T10:01:11Zoai: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:34982025-09-03 10:01:11.714CONICET 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 |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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