Melnikov Mikhail, Lopatina Anna, Sviridova Anastasiya, Chugunov Dmitriy, Vavilis Theofanis, Stamatellos Vasileios-Periklis, Stamoula Eleni, Cosentino Marco
Laboratory of Neuroimmunology, Federal Center of Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of Russia, Moscow, Russia; Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Moscow, Russia; Laboratory of Clinical Immunology, National Research Center Institute of Immunology of the Federal Medical-Biological Agency of Russia, Moscow, Russia.
Laboratory of Neuroimmunology, Federal Center of Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of Russia, Moscow, Russia; Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Moscow, Russia.
Asian J Psychiatr. 2025 Aug;110:104629. doi: 10.1016/j.ajp.2025.104629. Epub 2025 Jul 15.
Schizophrenia is a severe mental disorder associated with behavioural, cognitive, and emotional impairments. There are several leading theories on schizophrenia etilology, including genetic, neurotransmitter (dopamine and GABA-glutamate are the leading ones), immunological (microglial, cytokine, kynurenine) and neurodevelopmental (neuro-ontogenetic and neurodegenerative) theories. Despite the fact that in recent decades, the greatest efforts have been directed towards testing and developing genetic and neurotransmitter (including dopamine) theories, the recent evidence suggests that immunological aspects, in particular neuroinflammation (cytokine hypothesis) may play an important role in schizophrenia. Neuroinflammation in schizophrenia is thought to be mediated primarily by the activation of resident immune cells such as microglia. However, peripheral immune cells, which migrate through the blood-brain barrier into the central nervous system (CNS) are also involved in the development of neuroinflammation. Among the infiltrating cells that cause neuroinflammation, CD4 T helper (Th) 17 cells attract the most attention. These cells produce proinflammatory cytokines, increase the permeability of the blood-brain barrier, and activate resident microglia. The critical role of Th17 cells in the development of demyelinating and neurodegenerative diseases of the CNS has been established. In addition, the pathogenic role of Th17 cells in mental disorders such as depression and general anxiety disorder has also been demonstrated. In this report, we reviewed the recent evidence supporting the involvement of the Th17 cells in the pathogenesis of schizophrenia. Based on in vivo and in vitro studies, we suggest that Th17 cells could be considered as a promising additional therapeutic target in schizophrenia and deserve further investigation.
精神分裂症是一种与行为、认知和情感障碍相关的严重精神疾病。关于精神分裂症的病因学有几种主要理论，包括遗传学、神经递质（多巴胺和GABA-谷氨酸是主要的）、免疫学（小胶质细胞、细胞因子、犬尿氨酸）和神经发育（神经发生和神经退行性）理论。尽管近几十年来，最大的努力都致力于检验和发展遗传学和神经递质（包括多巴胺）理论，但最近的证据表明，免疫学方面，特别是神经炎症（细胞因子假说）可能在精神分裂症中起重要作用。精神分裂症中的神经炎症被认为主要由常驻免疫细胞如小胶质细胞的激活介导。然而，通过血脑屏障迁移到中枢神经系统（CNS）的外周免疫细胞也参与神经炎症的发展。在引起神经炎症的浸润细胞中，CD4 T辅助（Th）17细胞最受关注。这些细胞产生促炎细胞因子，增加血脑屏障的通透性，并激活常驻小胶质细胞。Th17细胞在中枢神经系统脱髓鞘和神经退行性疾病发展中的关键作用已经确立。此外，Th17细胞在抑郁症和广泛性焦虑症等精神障碍中的致病作用也已得到证实。在本报告中，我们回顾了支持Th17细胞参与精神分裂症发病机制的最新证据。基于体内和体外研究，我们认为Th17细胞可被视为精神分裂症一个有前景的额外治疗靶点，值得进一步研究。
