The role of neuroinflammation in schizophrenia: Focus on Th17 cells functions

Abstract

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.