Reduced regulatory T cells are associated with higher levels of Th1/TH17 cytokines and activated MAPK in type 1 bipolar disorder

Prado, Carine Hartmann do; Rizzo, Lucas B.; Wieck, Andréa; Lopes, Rodrigo Pestana; Teixeira, Antônio Lúcio; Grassi‐Oliveira, Rodrigo; Bauer, Moisés Evandro

doi:10.1016/j.psyneuen.2012.08.005

Cited by 104 publications

(76 citation statements)

References 50 publications

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“…In contrast, we were not able to confirm alterations in the expression of the major T-regulatory markers (that is, CD25 and foxp3 ) previously reported. 56 However, in this perspective, downregulated tgf β may cause a functional impairment of these cells, being released by a variety of leukocytes including T-reg cells.…”

Section: Discussionmentioning

confidence: 99%

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

et al. 2014

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We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfβ (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.

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Section: Discussionmentioning

confidence: 99%

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

et al. 2014

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“…We observed several age-related changes in peripheral lymphocyte subsets in RA including a significant drop in B cells (-41%) as well as the expansion of regulatory T cells (Tregs) (73%), CD4+CD28- T cells (81%) and CD8+CD28- T cells (38%). The loss of expression of the CD28 molecule is a major phenotypic T cell change during healthy aging as well as with multiple sclerosis, bipolar disorder and RA [15,37,38,39]. The loss of CD28 expression occurs in both CD4+ and CD8+ T cells but is more common in CD8+ T cells [14].…”

Section: Discussionmentioning

confidence: 99%

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

Petersen

Grassi‐Oliveira

Siara

et al. 2014

Neuroimmunomodulation

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Background: Rheumatoid arthritis (RA) has been associated with premature immunosenescence and an increased prevalence of age-related morbidities including poor cognitive function. Objective: We explored the relationships among lymphocyte subsets and memory in RA. Methods: Thirty patients with RA and 19 age-matched healthy controls took part in this study. Cognitive function stress and depression scores were evaluated by structured clinical questionnaires. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate the following subsets: B cells, activated and naïve/memory T cells, regulatory FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T cells. Results: RA patients were more depressed than controls, but stress levels were similar in the 2 groups. Patients had impaired memory performance compared to controls, demonstrated by lower Mini-Mental State Examination scores and logical and working memories (all p < 0.0001). These group effects remained significant after correcting for depression and age. Patients had expansion of regulatory T cells, naïve CD4+ T cells and CD8+CD28- cells but reduced percentages of B cells and memory CD8+CD45RO+ T cells compared to controls. CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with memory. Conclusion: RA patients had reduced memory performance compared to healthy controls. Expansion of activated and senescence-associated T cells was correlated with poor memory performance.

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“…Cognition usually demands high levels of energy supply, making cognitive functions particularly vulnerable to mitochondrial dysfunction and oxidative imbalance (Asevedo et al, 2012;Brietzke et al, 2011;Wood et al, 2009). Inflammation has also been shown to impact cognition in some illnesses such as AD, Major Depressive Disorder and Bipolar Disorder (do Prado et al, 2013;Grassi-Oliveira et al, 2011). In addition, there are preliminary evidences from one study that the chemokine CCL-2/MCP-1 is related to cognitive performance in individuals with psychosis .…”

Section: Introductionmentioning

confidence: 99%

Impact of peripheral levels of chemokines, BDNF and oxidative markers on cognition in individuals with schizophrenia

Asevedo

Gadelha

Noto

et al. 2013

Journal of Psychiatric Research

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Reduced regulatory T cells are associated with higher levels of Th1/TH17 cytokines and activated MAPK in type 1 bipolar disorder

Cited by 104 publications

References 50 publications

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

Impact of peripheral levels of chemokines, BDNF and oxidative markers on cognition in individuals with schizophrenia

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