Abstract
Aim
To investigate whether circulating T cells including regulatory T cells (Treg) and derived cytokines contribute to the immune imbalance observed in schizophrenia.
Methods
Forty patients with schizophrenia and 40 age, sex, body mass index, education, and smoking status–matched healthy controls (HC) are included in the study. We stained cells with anti-CD14, anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD20, and anti-CD16/56. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with the human FoxP3 kit containing anti-CD4/anti-CD25 and intracellular anti-Foxp3. PBMCs were cultured for 72 h and stimulated with anti-CD3/anti-CD28. Cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured from the culture supernatant and plasma using the Th1/Th2/Th17 cytokine bead array kit.
Results
In comparison with HC, Treg percentages in schizophrenia were higher (1.17 ± 0.63 vs 0.81 ± 0.53, P = 0.005) in unstimulated but lower in the stimulated condition (0.73 ± 0.69 vs 0.97 ± 0.55, P = 0.011). Activated T cell percentages were higher in schizophrenia than HC in unstimulated (2.22 ± 0.78 vs 1.64 ± 0.89, P = 0.001) and stimulated (2.25 ± 1.01 vs 1.72 ± 1.00, P = 0.010) conditions. The culture supernatant levels of IL-6 (7505.17 ± 5170.07 vs 1787.81 ± 1363.32, P < 0.001), IL-17A (191.73 ± 212.49 vs 46.43 ± 23.99, P < 0.001), TNF-α (1557 ± 1059.69 vs 426.57 ± 174.62, P = 0.023), and IFN-γ (3204.13 ± 1397.06 vs 447.79 ± 270.13, P < 0.001); and plasma levels of IL-6 (3.83 ± 3.41vs 1.89 ± 1.14, P = 0.003) and IL-17A (1.20 ± 0.84 vs 0.83 ± 0.53, P = 0.033) were higher in patients with schizophrenia than HC.
Conclusion
Our explorative study shows reduced level of Foxp3 expressing Treg in a stimulated condition with induced levels of proinflammatory cytokines in patients with schizophrenia.
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Cigdem Sahbaz, MD, managed the conceptualization, literature searches, statistical analyses, and designing figures and wrote the first draft of the manuscript; Tunc Akkoc, PhD, planned and managed experimental analysis; Sinan Guloksuz, MD, PhD, supervised interpreting the data and writing. All authors contributed to and approved the final manuscript.
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The Medical Ethical Review Committee of the Bezmialem Vakif University approved the study, which was conducted according to the latest version of the Declaration of Helsinki. Written informed consent was obtained from all participants.
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Sahbaz, C., Zibandey, N., Kurtulmus, A. et al. Reduced regulatory T cells with increased proinflammatory response in patients with schizophrenia. Psychopharmacology 237, 1861–1871 (2020). https://doi.org/10.1007/s00213-020-05504-0
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DOI: https://doi.org/10.1007/s00213-020-05504-0