Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses
Summary 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...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v162_n6_p1338_Farez http://hdl.handle.net/20.500.12110/paper_00928674_v162_n6_p1338_Farez |
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paper:paper_00928674_v162_n6_p1338_Farez2023-06-08T15:08:26Z Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses CCAAT enhancer binding protein alpha interleukin 10 melatonin mitogen activated protein kinase 1 mitogen activated protein kinase 3 retinoid related orphan receptor alpha retinoid related orphan receptor gamma transcription factor transcription factor Nfil3 unclassified drug basic leucine zipper transcription factor CCAAT enhancer binding protein melatonin retinoid related orphan receptor gamma adult animal cell animal experiment animal model Article autumn cell differentiation controlled study disease activity enzyme activation experimental allergic encephalitis female human human cell major clinical study male mouse multiple sclerosis nonhuman priority journal protein expression regulatory T lymphocyte seasonal variation Th17 cell transactivation winter animal C57BL mouse cytology experimental autoimmune encephalomyelitis immunology light metabolism multiple sclerosis pathology recurrent disease season signal transduction Animals Basic-Leucine Zipper Transcription Factors CCAAT-Enhancer-Binding Proteins Cell Differentiation Encephalomyelitis, Autoimmune, Experimental Female Humans Light Male MAP Kinase Signaling System Melatonin Mice Mice, Inbred C57BL Multiple Sclerosis Nuclear Receptor Subfamily 1, Group F, Member 3 Recurrence Seasons T-Lymphocytes, Regulatory Th17 Cells Summary 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. © 2015 Elsevier Inc. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v162_n6_p1338_Farez http://hdl.handle.net/20.500.12110/paper_00928674_v162_n6_p1338_Farez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
CCAAT enhancer binding protein alpha interleukin 10 melatonin mitogen activated protein kinase 1 mitogen activated protein kinase 3 retinoid related orphan receptor alpha retinoid related orphan receptor gamma transcription factor transcription factor Nfil3 unclassified drug basic leucine zipper transcription factor CCAAT enhancer binding protein melatonin retinoid related orphan receptor gamma adult animal cell animal experiment animal model Article autumn cell differentiation controlled study disease activity enzyme activation experimental allergic encephalitis female human human cell major clinical study male mouse multiple sclerosis nonhuman priority journal protein expression regulatory T lymphocyte seasonal variation Th17 cell transactivation winter animal C57BL mouse cytology experimental autoimmune encephalomyelitis immunology light metabolism multiple sclerosis pathology recurrent disease season signal transduction Animals Basic-Leucine Zipper Transcription Factors CCAAT-Enhancer-Binding Proteins Cell Differentiation Encephalomyelitis, Autoimmune, Experimental Female Humans Light Male MAP Kinase Signaling System Melatonin Mice Mice, Inbred C57BL Multiple Sclerosis Nuclear Receptor Subfamily 1, Group F, Member 3 Recurrence Seasons T-Lymphocytes, Regulatory Th17 Cells |
| spellingShingle |
CCAAT enhancer binding protein alpha interleukin 10 melatonin mitogen activated protein kinase 1 mitogen activated protein kinase 3 retinoid related orphan receptor alpha retinoid related orphan receptor gamma transcription factor transcription factor Nfil3 unclassified drug basic leucine zipper transcription factor CCAAT enhancer binding protein melatonin retinoid related orphan receptor gamma adult animal cell animal experiment animal model Article autumn cell differentiation controlled study disease activity enzyme activation experimental allergic encephalitis female human human cell major clinical study male mouse multiple sclerosis nonhuman priority journal protein expression regulatory T lymphocyte seasonal variation Th17 cell transactivation winter animal C57BL mouse cytology experimental autoimmune encephalomyelitis immunology light metabolism multiple sclerosis pathology recurrent disease season signal transduction Animals Basic-Leucine Zipper Transcription Factors CCAAT-Enhancer-Binding Proteins Cell Differentiation Encephalomyelitis, Autoimmune, Experimental Female Humans Light Male MAP Kinase Signaling System Melatonin Mice Mice, Inbred C57BL Multiple Sclerosis Nuclear Receptor Subfamily 1, Group F, Member 3 Recurrence Seasons T-Lymphocytes, Regulatory Th17 Cells Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses |
| topic_facet |
CCAAT enhancer binding protein alpha interleukin 10 melatonin mitogen activated protein kinase 1 mitogen activated protein kinase 3 retinoid related orphan receptor alpha retinoid related orphan receptor gamma transcription factor transcription factor Nfil3 unclassified drug basic leucine zipper transcription factor CCAAT enhancer binding protein melatonin retinoid related orphan receptor gamma adult animal cell animal experiment animal model Article autumn cell differentiation controlled study disease activity enzyme activation experimental allergic encephalitis female human human cell major clinical study male mouse multiple sclerosis nonhuman priority journal protein expression regulatory T lymphocyte seasonal variation Th17 cell transactivation winter animal C57BL mouse cytology experimental autoimmune encephalomyelitis immunology light metabolism multiple sclerosis pathology recurrent disease season signal transduction Animals Basic-Leucine Zipper Transcription Factors CCAAT-Enhancer-Binding Proteins Cell Differentiation Encephalomyelitis, Autoimmune, Experimental Female Humans Light Male MAP Kinase Signaling System Melatonin Mice Mice, Inbred C57BL Multiple Sclerosis Nuclear Receptor Subfamily 1, Group F, Member 3 Recurrence Seasons T-Lymphocytes, Regulatory Th17 Cells |
| description |
Summary 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. © 2015 Elsevier Inc. |
| title |
Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses |
| 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 |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v162_n6_p1338_Farez http://hdl.handle.net/20.500.12110/paper_00928674_v162_n6_p1338_Farez |
| _version_ |
1768546533421088768 |