Format

Send to

Choose Destination
Cell. 2015 Sep 10;162(6):1338-52. doi: 10.1016/j.cell.2015.08.025.

Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.

Author information

1
Center for Research on Neuroimmunological Diseases (CIEN), Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires 1428, Argentina. Electronic address: mfarez@fleni.org.ar.
2
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (IBYME-CONICET), Buenos Aires 1428, Argentina.
4
Center for Research on Neuroimmunological Diseases (CIEN), Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires 1428, Argentina; Department of Neurology, Hospital de Clínicas José de San Martín, Buenos Aires 1428, Argentina.
5
Center for Research on Neuroimmunological Diseases (CIEN), Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires 1428, Argentina.
6
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
7
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (IBYME-CONICET), Buenos Aires 1428, Argentina; Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina.
8
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: fquintana@rics.bwh.harvard.edu.

Abstract

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.

PMID:
26359987
PMCID:
PMC4570563
DOI:
10.1016/j.cell.2015.08.025
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center