Melatonin role in formation of T helper subpopulations co-expressing Th17 and Treg markers

Abstract

BACKGROUND: One of the main pineal hormones, melatonin, has multifunctional activity including ability to effectively regulate immune cells. Subpopulations of Th17 (T helpers producing interleukin 17) and Treg (regulatory T cells) are under the hormone direct control. It has now been established that both subpopulations are heterogeneous, have high plasticity, and non-classical Th17/Treg variants play leading role in the pathogenesis of various diseases.

AIM: To evaluate exogenous melatonin effects on classical Th17 and Treg subpopulations, as well as non-classical population of cells co-expressing Th17 and Treg markers.

METHODS: The objects of the study were leukocytes of healthy donors. Differentiation of Th17 and Treg was assessed in vitro in response to polyclonal activation (anti-CD3/CD28) by the presence and level of corresponding markers using flow cytometry. The role of specific receptors in melatonin-dependent regulation of Treg and Th17 was determined by inhibitory analysis.

RESULTS: It has been shown that the hormone in concentration corresponding to its level in peripheral blood during pharmacological usage is able not only to regulate formation of classical Th17 and Treg populations by suppressing the differentiation of CD4⁺FOXP3⁺ cells, but also to induce formation of T lymphocytes that simultaneously express Th17 and Treg cells’ markers.

CONCLUSION: The effects of melatonin on both classical Th17 and Treg populations and non-classical one lead to a shift in the balance towards Th17 cells, which may contribute to inflammation development in various pathological situations.

Keywords

Th17 / Treg / CD4+RORγt+FOXP3+ T cells / melatonin / melatonin receptors

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