MELATONIN RECEPTORS MT1/MT2 IN PROINFLAMMATORY T-HELPER POPULATIONS

Abstract

Objective. The pineal hormone melatonin is an effective regulator of the main T helper populations Th1 and Th17. Currently, the focus of attention in the study of T helpers is shifting from classical to non-classical variants of these cells, primarily to Th1-polarized lymphocytes Th17 (Th17.1), which are formed in vitro and in vivo by transforming differentiated Th17 cells into Th1 under polarizing conditions. Th17.1 cells have a significantly higher pro-inflammatory potential compared to classical Th1/Th17 and play a key role in the pathogenesis of Th-dependent pro-inflammatory diseases, including autoimmune diseases. Tasks. This shift in priorities in the study of T helper activity raises the question of the sensitivity of non-classical pathogenic CD4⁺Т lymphocytes to melatonin-dependent regulation, which is largely determined by the expression of high-affinity receptors for the hormone, MT1 and MT2, on the cell membrane. Materials and methods. In this work, we studied the expression of MT1 and MT2 by proinflammatory T-helper populations of peripheral blood. Results. It was shown that non-classical Th1-polarized Th17 cells have a selectively high level of expression of these receptors, which makes them a priority target for the action of melatonin. Discussion and conclusions. It is important to note that MT1 and MT2 exert their effects primarily through inhibitory G proteins (Gi), suppressing adenylate cyclase activity, and, to a lesser extent, through Gq and Go proteins, activating phospholipase C, calcium channels, and mitogen-activated protein kinases. Moreover, all of the listed signaling pathways, launched when melatonin binds to membrane melatonin receptors, are stimulating or costimulating for T cells. In this regard, it is logical to expect a stimulatory effect of melatonin on the pathogenic Th17.1 population. However, melatonin has not only a membrane but also a nuclear receptor, RORα (an obligate molecule for Th17 cells – both classical and non-classical), and at micromolar concentrations is able to bind to additional intracellular targets, such as calmodulin or hydroquinone, and trigger other signaling mechanisms that can correct MT1/MT2-dependent signals.