Melatonin signaling in T cells: Functions and applications

Abstract

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

T Cells in Osteoarthritis: Alterations and Beyond

“…Under the stimulation of interleukin (IL)-12, naïve CD4 + T cells differentiate into Th1 cells, which produce IL-2, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, lymphotoxins, and granulocyte-macrophage colony-stimulating factor (42–44). Most current evidence indicates that Th1 cells do not alter significantly on entering the peripheral blood of OA patients.…”

“…When stimulated by IL-4, naïve CD4 + T cells differentiate into Th2 cells (44). Through the production of IL-4, IL-5, IL-10, and IL-13, Th2 cells affect the function of B cells, dendritic cells, eosinophils, etc.…”

Responses of Transgenic Melatonin-Enriched Goats on LPS Stimulation and the Proteogenomic Profiles of Their PBMCs

“…At the cellular level, microarray analysis of gene expression also confirmed the anti-inflammatory effects of MT on Raw 264.7 cells stimulated by LPS [37]. The effect of MT on immune biology is mediated by its receptors or by receptor-independent pathways [38]. MT suppresses the LPS-induced increase in lipid peroxidation in both in vivo and in vitro animal models [39].…”

A circadian based inflammatory response – implications for respiratory disease and treatment

“…Melatonin is thought to have an immuno-modulatory role that can either be pro or anti-inflammatory however the mechanism is still unclear. Different studies showing the actions of endogenous and exogenous melatonin on the immune system have been reviewed elsewhere (Carrillo-Vico et al 2005;Carrillo-Vico et al 2013;Ren et al 2017). Nevertheless it is worth mentioning the review by Carrillo-Vico and co-authors suggesting that melatonin may act as an immune buffer, whereby it may act as an immune stimulant under immune suppressive conditions and as an antiinflammatory agent under conditions of exacerbated inflammation (Carrillo-Vico et al 2013).…”