Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance

Álvarez-Sánchez, Nuria; Cruz‐Chamorro, Ivan; López-González, Antonio; Utrilla, José C.; Fernández-Santos, José M.; Martínez‐López, Alicia; Lardone, Patricia Judith; Guerrero, Juan M.; Carrillo-Vico, Antonio

doi:10.1016/j.bbi.2015.06.021

Cited by 88 publications

(108 citation statements)

References 73 publications

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“…Additionally, melatonin has been reported as a potential inducer of Th17 response . In contrast, others authors indicate that melatonin treatment decreases the intracellular levels of IL‐17A . In the present study, melatonin treatment showed a rising trend in production of IL‐17A cytokines in T. cruzi‐ infected and melatonin‐treated animals.…”

Section: Discussioncontrasting

confidence: 62%

Interleukin‐17, oxidative stress, and inflammation: role of melatonin during Trypanosoma cruzi infection

Brazão

Colato

Santello

et al. 2015

Journal of Pineal Research

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Although the exact etiology of Chagas' disease remains unknown, the inflammatory process and oxidative stress are believed to be the main contributors to the dysfunction and pathogenesis during chronic Trypanosoma cruzi infection. Our hypothesis is that melatonin administered for 2 months daily could modulate the oxidative stress and the inflammatory response during the chronic infection. Flow cytometric analysis of macrophages and antigen-presenting cells (APC), expression of RT1B as well as LFA-1 and MCP-1 in CD4(+) and CD8(+) T cells and levels of interleukin-17A were assessed. The oxidative stress was evaluated through lipid peroxidation (LPO) analysis on the plasma of thiobarbituric acid-reactive substances (TBARS) and nitric oxide production. Decreased concentrations of nitrite and TBARS were found in infected and melatonin-treated animals, as well as a rising trend in the production of IL-17A as compared to infected and untreated counterparts. A significant decrease was found in the percentages of CD4(+) and CD8(+) T lymphocytes MCP-1 producers for infected and melatonin-treated rats. Reduced percentage of CD8(+) T cells producing LFA-1 was observed in control and melatonin-treated animals as compared to untreated rats. The cellular response of peritoneal APC cells and macrophages significantly dropped in infected and treated animals. As an endpoint, the use of antioxidant compounds such as melatonin emerges as a new and promising approach to control the oxidative stress during the chronic Chagas' disease partially mediated through the abrogation of LPO and the prevention of the inflammatory response and can be used for further investigation on treatment trials for other infectious diseases.

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Section: Discussioncontrasting

confidence: 62%

Interleukin‐17, oxidative stress, and inflammation: role of melatonin during Trypanosoma cruzi infection

Brazão

Colato

Santello

et al. 2015

Journal of Pineal Research

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“…Melatonin significantly lowers the level of IFN‐γ, but enhances the secretion of IL‐4 and IL‐10 from anti‐CD3 antibody‐stimulated Th cells in the presence of mitomycin C‐treated splenocytes . When the mononuclear cells derived from mouse lymph nodes were stimulated with pMOG in vitro, melatonin significantly decreased the frequency of TNF + CD4 + cells, although it was without effect on the frequencies of IL‐17 + CD4 + and IFN‐γ + CD4 + cells . Melatonin lowers the production IFN‐γ, TNF, IL‐5, IL‐9, and IL‐1β in PBMCs from healthy individuals, although it has almost no effect on production of those cytokines in PBMCs from patients with SLE .…”

Section: Melatonin and Differentiation Of T Cellsmentioning

confidence: 99%

Melatonin signaling in T cells: Functions and applications

Ren

Liu

Chen

et al. 2017

Journal of Pineal Research

181

130

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Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status, and immune function. Importantly, melatonin significantly influences T-cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T-cell biology and the beneficial effects of melatonin in T-cell response-based diseases. In addition to expressing both membrane and nuclear receptors for melatonin, T cells have the four enzymes required for the synthesis of melatonin and produce high levels of melatonin. Meanwhile, melatonin is highly effective in modulating T-cell activation and differentiation, especially for Th17 and Treg cells, and also memory T cells. Mechanistically, the influence of melatonin in T-cell biology is associated with membrane and nuclear receptors as well as receptorindependent pathways, for example, via calcineurin. Several cell signaling pathways, including ERK1/2-C/EBPα, are involved in the regulatory roles of melatonin in Tcell biology. Through modulation in T-cell responses, melatonin exerts beneficial effects in various inflammatory diseases, such as type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. These findings highlight the importance of melatonin signaling in T-cell fate determination, and T cell-based immune pathologies. K E Y W O R D Smelatonin, multiple sclerosis, systemic lupus erythematosus, T cells, Th17 cells, Treg cells

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“…In MS, melatonin levels negatively correlate with disease activity, most likely via blockade of Th17 and induction of Tr1 differentiation via Nfil3 and Erk1/2, respectively 34 . Its therapeutic potential has been demonstrated in the animal model of MS (Experimental autoimmune encephalomyelitis, EAE) 34–36 and in in vitro studies using peripheral blood mononuclear cells (PBMCs) from MS patients and healthy controls, in which melatonin improves impaired antioxidant defense through upregulation of sirtuin 1 and antioxidant enzymes 37 . Given its antioxidant properties, which are relevant to neurodegeneration and demyelination 38 , melatonin might be an interesting therapeutic target for the treatment of both active and progressive stages of MS and thus worthy of further experimental and clinical study.…”

Section: Geographic Factors and Sun Exposurementioning

confidence: 99%

Environmental control of autoimmune inflammation in the central nervous system

Rothhammer

Quintana

2016

Current Opinion in Immunology

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Summary Multiple Sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which causes severe disability and requires extensive medical attention and treatment. While the infiltration of pathogenic immune cells into the CNS leads to the formation of inflammatory lesions in its initial relapsing-remitting stage, late stages of MS are characterized by progressive neuronal loss and demyelination even without continued interaction with the peripheral immune compartment. Several genetic and environmental factors modulate and influence these processes on multiple levels. Genetic variants confer a predisposition for the development of MS, but are not accessible to therapeutic intervention as of today. However, migration studies suggest that environmental factors influence disease development, activity and progression. This article reviews mechanisms of disease pathogenesis in MS and their modulation by environmental factors such as geographical localization, the gut microbiome and the diet.

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Melatonin controls experimental autoimmune encephalomyelitis by altering the T effector/regulatory balance

Cited by 88 publications

References 73 publications

Interleukin‐17, oxidative stress, and inflammation: role of melatonin during Trypanosoma cruzi infection

Interleukin‐17, oxidative stress, and inflammation: role of melatonin during Trypanosoma cruzi infection

Melatonin signaling in T cells: Functions and applications

Environmental control of autoimmune inflammation in the central nervous system

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