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.

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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We investigated the role of epiphyseal hormone melatonin in the differentiation of naive CD4+T cells into regulatory T cells (Treg). The hormone at physiological and pharmacological concentrations inhibited Treg differentiation, decreasing both the proportion of CD4+FOXP3+ cells in the culture and the level of TGF‑β, the key cytokine for this T cell subpopulation. The inhibitory effect of exogenous melatonin was due to its interaction with the membrane receptors MT1 and MT2. At the same time, the signals realized through RORa — the nuclear receptor for melatonin — stimulated Treg formation; however, they were considerably weaker than the signals from the membrane receptors and were overlapped by the latter. Since the Treg subpopulation plays an important role in physiological and pathological processes in the body, the revealed effects of melatonin should be taken into account in its therapeutic use.

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