We studied the ability of melatonin in physiological and pharmacological concentrations to induce and/or regulate differentiation of T cells producing IL-17 (Th17). This hormone produced the opposite effect on CD4+T cells, which depended on their activation status. Melatonin induced the synthesis of IL-17A by intact T cells, but had little effect on activated cells. Melatonin in high (pharmacological) concentration decreased the intracellular expression of this cytokine under conditions of polyclonal activation. Melatonin had a dose-depended effect. Taking into the fact that Th17 cells play an important role in the immune defense, it can be suggested that the regulation of their activity by melatonin contributes to this process.
Anergy is a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of IL-2 production and proliferation. Anergy is a pathway of peripheral tolerance formation. In this review, mechanisms underlying T-cell tolerization are considered in a classical in vitro model of clonal anergy, and these mechanisms are compared with different pathways of anergy induction in vivo. Special attention is given to regulatory T-lymphocytes because, on one hand, anergy is a specific feature of these cells, and on the other hand anergy is also a mechanism of their action on target cells - effector T-lymphocytes. The role of this phenomenon in the differentiation of regulatory T-cells and also in the development of activation-induced apoptosis in effector T-lymphocytes is discussed.
We studied the role of endogenous melatonin in the development and functioning of T cells that produce IL-17 (Th17) and regulatory T cells (Treg) during pregnancy. The study was performed ex vivo and in vitro with auto-serum as the source of endogenous melatonin under conditions of blockade of melatonin-dependent signaling. Participation of the hormone in the regulation of differentiation of both CD4RORγt and CD4FoxP3T cells and their key products IL-17A and TGF-β was demonstrated. It is known that the normal gestational process is accompanied by a decrease in Th17/Treg ratio due to hormonal changes. The sensitivity of the studied subpopulations to melatonin during pregnancy can affect its outcome.
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