MT1/MT2 melatonin receptors in proinflammatory T helper cell populations
- 作者: Kuklina E.M.1, Danchenko I.Y.2, Baidina T.V.2
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隶属关系:
- Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences
- Perm State Medical University named after E.A. Wagner of the Ministry of Healthcare of the Russian Federation
- 期: 卷 28, 编号 3 (2025)
- 页面: 375-380
- 栏目: SHORT COMMUNICATIONS
- URL: https://journal-vniispk.ru/1028-7221/article/view/319871
- DOI: https://doi.org/10.46235/1028-7221-17120-MMM
- ID: 319871
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详细
Melatonin, a pineal gland hormone, is an effective regulator of the main T helper Th1 and Th17 populations. Currently, the studies of T helpers are shifting from classical to non-classical variants of these cells, primarily to Th1-polarized Th17 lymphocytes (Th17.1), which are formed in vitro and in vivo by transformation of 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 pathogenesis of Th-dependent pro-inflammatory disorders, including autoimmune diseases. Such a shift in priorities in the study of T helper activity raises the issue of sensitivity of non-classical pathogenic CD4+T lymphocytes to melatonin-dependent regulation, which is largely determined by the cell membrane expression of high-affinity MT1 and MT2 melatonin receptors. Materials and methods. In this work, we studied the expression of MT1 and MT2 at the proinflammatory T helper populations in peripheral blood. Results. It was shown that non-classical Th1-polarized Th17 cells have a selectively high level of expression of these receptors, thus making them a priority target for the action of melatonin. Discussion and conclusions. Worth of note, MT1 and MT2 exert their effects, mainly, via inhibitory G proteins (Gi), suppressing the activity of adenylate cyclase, and, to a lesser extent, through Gq and Go proteins, activating phospholipase C, calcium channels and mitogen-activated protein kinases. Moreover, all these signaling pathways triggered by melatonin binding to specific membrane receptors are stimulatory or co-stimulatory for T cells. In this regard, one could expect a stimulatory effect of melatonin on the pathogenic Th17.1 population. However, melatonin receptors are not only on membrane, but also in target cell unclear. E.g., RORα (an obligate molecule for Th17 cells, both classical and non-classical) is able to bind at micromolar amounts to additional intracellular targets, such as calmodulin or hydroquinone, and trigger other signaling mechanisms that may correct MT1/MT2-dependent signals.
作者简介
Elena Kuklina
Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences
编辑信件的主要联系方式.
Email: ibis_07@mail.ru
ORCID iD: 0000-0002-2173-2724
PhD, MD (Biology), Leading Researcher, Laboratory of Immunoregulation
俄罗斯联邦, PermIrina Danchenko
Perm State Medical University named after E.A. Wagner of the Ministry of Healthcare of the Russian Federation
Email: irene-dan@mail.ru
ORCID iD: 0000-0002-3145-5409
PhD (Medicine), Assistant Professor, Department of Neurology and Medical Genetics
俄罗斯联邦, PermTatiana Baidina
Perm State Medical University named after E.A. Wagner of the Ministry of Healthcare of the Russian Federation
Email: tatiana_baidina@mail.ru
ORCID iD: 0000-0002-5114-0463
PhD, MD (Medicine), Professor, Department of Neurology and Medical Genetics
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