Plasma IL-17A levels in patients with late-life depression

Saraykar, Smita; Cao, Bo; Barroso, Lucélia Scarabeli Silva; Pereira, Kelly Silva; Bertola, Laiss; Nicolau, Mariana de Souza; Ferreira, Jéssica Diniz Rodrigues; Dias, Natália Silva; Vieira, Érica Leandro Marciano; Teixeira, Antônio Lúcio; Silva, Ana Paula M.; Diniz, Breno S.

doi:10.1590/1516-4446-2017-2299

Cited by 18 publications

(14 citation statements)

References 21 publications

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“…One study found a decrease in the number of T H 17 cells in depressed subjects compared to age and gender-matched healthy controls, but also found a decrease in the number of T reg cells from depressed subjects when the sample was restricted to those over 28 years of age (Grosse et al, 2016). Others have found no differences in plasma levels of IL-17A between a group with late-life depression and a group of healthy matched controls (Saraykar et al, 2017), or a decreased level of IL-17A in patients with recurrent depressive disorder (Rybka, 2013). This seemingly contradictory literature, in both animals and humans, may perhaps be explained by differences between acute depressive symptoms and those of chronic depression, which some have posited represent two different states of immune regulation, with activation at the time of acute symptoms and suppression in the face of chronic symptoms (Hong et al, 2013).…”

Section: Depressionmentioning

confidence: 95%

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders

Osborne

Brar

Klein

2019

Brain, Behavior, and Immunity

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T cells play a key role in adaptive immune responses, and shifts among T cell classes occur in normal pregnancy. There is evidence for the role of T H 17 cells and dysregulation of the T H 17:T reg cell balance in morbidities and autoimmune diseases during pregnancy. Because T H 17 responses may play a role in depression and anxiety outside of pregnancy, we hypothesize that T H 17 responses and the balance of T H 17:T reg activity may also contribute to the development of depression and anxiety during pregnancy. To explore this hypothesis, this review has three main aims: 1) to evaluate systematically the role of T H 17 cells and cytokines during pregnancy; 2) to compare changes in the ratio of T H 17:T reg cells during pregnancy morbidities with the changes that occur in depression and anxiety outside of pregnancy; and 3) to provide a basis for further research on T H 17 cells in perinatal mood and anxiety disorders, with an eye toward the development of novel therapeutics. We also review the limited literature concerning perinatal mood and anxiety disorders, and hypothesize about the potential role of T H 17 cells in these illnesses. Understanding the pathophysiology of perinatal mood and anxiety disorders will aid development of novel therapeutics that address immunological mechanisms, in addition to the serotonin system, which are targetable molecules in treating depression and anxiety during pregnancy.

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Section: Depressionmentioning

confidence: 95%

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders

Osborne

Brar

Klein

2019

Brain, Behavior, and Immunity

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“…There are several studies showing that IL-17A levels are not associated with depressive symptoms (Liu et al, 2012;Kim et al, 2013;Spanemberg et al, 2014). For example, Saraykar hypothesized that there is no correlation between IL-17A and depression in late life, but there is a possible association between IL-17A and cognitive dysfunction (Saraykar et al, 2018). This could suggest that Th17 cells may exert their effects in depression via cytokines other than IL-17, such as IL-21 and IL-22.…”

Section: Th17 Cells and Depressionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…The notion that Th17 cells play a critical role in the onset of depression has been growing in popularity but remains controversial. Several human studies have demonstrated that changes in IL-17 are correlated with depression 21,23,25,51 while others have not 20,24 . While further work is needed to fully understand the role of IL-17 in the onset of depressive symptoms, our work demonstrates that the AHR is not responsible for the observed stress-induced increase in intestinal Th17s and that these cells are not necessary for the induction of stress-induced depression.…”

Section: Discussionmentioning

confidence: 99%

“…Administration of IL-17A blocking antibodies has also been found to reduce learned helplessness behaviors in mice 17 . However, the evidence for the role of IL-17 in human depression remains controversial, with some reports claiming a positive correlation between the inflammatory cytokine and depression and others reporting no differences in IL-17 levels between those with the disease and controls [20][21][22][23][24][25] . These conflicting results highlight the need for further investigation into the mechanism and role of the AHR and increased inflammatory Th17 cells in depression.…”

Section: Introductionmentioning

confidence: 99%

Stress-Induced Despair Behavior Develops Independently of the AHR-RORgt Axis in CD4+ cells

Rivet-Noor¹,

Merchak²,

Li³

et al. 2022

Preprint

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Current treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have been observed in both clinical settings and in mouse models. As such, microbial supplements and probiotics have become a target for potential therapeutics. A current hypothesis for the mechanism of action of these supplements is via the aryl hydrocarbon receptor’s (AHR) modulation of the T helper 17 cell (Th17) and T regulatory cell axis. As inflammatory RORgt+ CD4+ Th17 T cells and their primary cytokine IL-17 have been implicated in the development of stress-induced depression, the connection between stress, the AHR, Th17s and depression remains critical to disease understanding. Here, we utilize genetic knockouts to examine the role of the microbial sensor AHR in the development of stress induced despair behavior. We observe an AHR-independent increase in gut-associated Th17s in stressed mice, indicating that AHR is not responsible for this communication. Further, we utilized a CD4-specific Rorc knockout line to disrupt the production of Th17s. Mice lacking Rorc induced IL-17 did not show any differences in behavior from controls before or after stress. Finally, we utilize an unsupervised machine learning system to examine minute differences in behavior that could not be observed in traditional behavioral assays. Our data demonstrate that neither CD4 specific Ahr nor Rorc are necessary for the development of stress-induced anxiety-or depressive-like behaviors. These data suggest that research approaches should focus on other sources or sites of IL-17 production in stress-induced depression.

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Plasma IL-17A levels in patients with late-life depression

Cited by 18 publications

References 21 publications

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders

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

Stress-Induced Despair Behavior Develops Independently of the AHR-RORgt Axis in CD4+ cells

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