Reduced regulatory T cells with increased proinflammatory response in patients with schizophrenia

Psychopharmacology (Berl). 2020 Jun;237(6):1861-1871. doi: 10.1007/s00213-020-05504-0. Epub 2020 Mar 27.

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.

Keywords: Adaptive immunity; FoxP3; IL-17A; Regulatory T cell; Schizophrenia; T cell.

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Inflammation Mediators / immunology*
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Interleukin-17 / blood
  • Interleukin-17 / immunology
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Male
  • Middle Aged
  • Schizophrenia / blood*
  • Schizophrenia / diagnosis
  • Schizophrenia / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • IL10 protein, human
  • IL17A protein, human
  • IL2RA protein, human
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Tumor Necrosis Factor-alpha
  • Interleukin-10