Molecular Mechanisms of Control of Differentiation of Regulatory T-Lymphocytes by Exogenous Melatonin

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 RORα-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.