Th17 Cells in Depression: Are They Crucial for the Antidepressant Effect of Ketamine?

Abstract

Background: Major depressive disorder is associated with inflammation and immune processes. Depressive symptoms correlate with inflammatory markers and alterations in the immune system including cytokine levels and immune cell function. Th17 cells are a T cell subset which exerts proinflammatory effects. Th17 cell accumulation and Th17/Treg imbalances have been reported to be critical in the pathophysiology of major depressive disorder and depressive-like behaviors in animal models. Th17 cells are thought to interfere with glutamate signaling, dopamine production, and other immune processes. Ketamine is a newly characterized antidepressant medication which has proved to be effective in rapidly reducing depressive symptoms. However, the mechanisms behind these antidepressant effects have not been fully elucidated.Method: Literature about Th17 cells and their role in depression and the antidepressant effect of ketamine are reviewed, with the possible interaction networks discussed.Result: The immune-modulating role of Th17 cells may participate in the antidepressant effect of ketamine.Conclusion: As Th17 cells play multiple roles in depression, it is important to explore the mechanisms of action of ketamine on Th17 cells and Th17/Treg cell balance. This provides new perspectives for strengthening the antidepressant effect of ketamine while reducing its side effects and adverse reactions.

Ordering Knowledge in the Markers of Psychiatric/Mental Disorders

“…Moreover, the HPA axis activation and its related anxiety are presented in most (up to ~80%) mood and psychotic disorders [20][21][22]. This is in line with recent findings that the anxiety-related Th17 cell response can be induced by the combination of IL-6 and TGF cytokines [7,23] and, therefore, by these cytokines, which seem to dominate in the depressive and psychotic states, respectively, and can be influenced by environmental factors/toxins [23]. It was also reported that the microbiota (especially extracellular intestinal bacteria/fungi) might influence the Th17 response and determine the pathogenesis of rheumatoid diseases [23] that often accompany stress symptoms [24], or it might be that Th17 could mimic such infection.…”

“…In anxiety disorders, there is also a serious hyperactivation of the proinflammatory state, which may be due to the increased activity of the HPA axis. In anxiety behaviour, the Th17 response may be crucial, and the observed Th1-Th17 engagement may be due to the HPA hyperactivation and mood changes that accompany anxiety [5][6][7][8].…”

Mood symptoms and chronic fatigue syndrome due to relapsing remitting multiple sclerosis are associated with immune activation and aberrations in the erythron

“…Previously, it was discussed how increased IL-17, IL-6 and TNF-α (the components of the Th17-axis in the current study) contribute to major depressive disorder and chronic fatigue symptoms (Al-Hakeim et al, 2022a;Cui et al, 2021;Kim et al, 2021;Maes and Carvalho, 2018;Morris, Gerwyn and Maes, Michael, 2013;Nadeem et al, 2017;Vieira et al, 2010). Interestingly, the first paper that reported increased TNF-α in major depression, found that the serum levels of this cytokine were higher in major depression than in MS (Mikova et al, 2001).…”

Inflammatory pathophysiological mechanisms implicated in postpartum depression

“…Meanwhile, some differences exist. In depression, Th17 cells are reported accumulated and the Th17/Treg cell balance was dysregulated ( Cui et al, 2021 ). Similar report has been declared in the study of depression and anxiety during pregnancy ( Osborne et al, 2019b ).…”