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Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4 + T-cell subsets in multiple sclerosis patients.
- Source :
-
European journal of immunology [Eur J Immunol] 2018 Aug; Vol. 48 (8), pp. 1376-1388. Date of Electronic Publication: 2018 Jun 06. - Publication Year :
- 2018
-
Abstract
- Excessive levels of proinflammatory cytokines in the CNS are associated with reduced serotonin (5-HT) synthesis, a neurotransmitter with diverse immune effects. In this study, we evaluated the ability of exogenous 5-HT to modulate the T-cell behavior of patients with MS, a demyelinating autoimmune disease mediated by Th1 and Th17 cytokines. Here, 5-HT attenuated, in vitro, T-cell proliferation and Th1 and Th17 cytokines production in cell cultures from MS patients. Additionally, 5-HT reduced IFN-γ and IL-17 release by CD8 <superscript>+</superscript> T cells. By contrast, 5-HT increased IL-10 production by CD4 <superscript>+</superscript> T cells from MS patients. A more accurate analysis of these IL-10-secreting CD4 <superscript>+</superscript> T cells revealed that 5-HT favors the expansion of FoxP3 <superscript>+</superscript> CD39 <superscript>+</superscript> regulatory T cells (Tregs) and type 1 regulatory T cells. Notably, this neurotransmitter also elevated the frequency of Treg17 cells, a novel regulatory T-cell subset. The effect of 5-HT in upregulating CD39 <superscript>+</superscript> Treg and Treg17 cells was inversely correlated with the number of active brain lesions. Finally, in addition to directly reducing cytokine production by purified Th1 and Th17 cells, 5-HT enhanced in vitro Treg function. In summary, our data suggest that serotonin may play a protective role in the pathogenesis of MS.<br /> (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Adult
Brain pathology
CD8-Positive T-Lymphocytes immunology
Cell Proliferation physiology
Cells, Cultured
Female
Humans
Lymphocyte Activation immunology
Male
Multiple Sclerosis immunology
Interferon-gamma metabolism
Interleukin-17 metabolism
Multiple Sclerosis pathology
Serotonin metabolism
T-Lymphocytes, Regulatory immunology
Th1 Cells immunology
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 48
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 29719048
- Full Text :
- https://doi.org/10.1002/eji.201847525