Aberrant Expression of TH2LCRR and GATA3 in Peripheral Blood Mononuclear Cells of Patients with Acute-Phase Schizophrenia: Integrative Bioinformatics Analysis and Experimental Study.

Abstract

Although evidence suggests that an imbalance in Th1 and Th2 cell responses contributes to the pathogenesis of schizophrenia, the epigenetic mechanisms involved remain largely unknown. Here, we applied a combination of bioinformatics and experimental approaches to evaluate the alterations in Th1 and Th2-related genes in schizophrenia patients. Based on bioinformatics analysis, we selected Th1 (IFNG-AS1, TBX21, IFNG) and Th2-related genes (TH2LCRR, GATA3, IL-4), which are potentially implicated in the pathogenesis of schizophrenia. For experimental validation, we measured the expression levels of these transcripts in peripheral blood mononuclear cells (PBMCs) from patients with acute-phase schizophrenia and controls. Bioinformatics findings revealed 2 lncRNAs, 9 miRNAs, 76 mRNAs, and 234 transcription factors (TFs) related to Th1 and Th2 cell lineages, which are involved in schizophrenia. Subsequent analysis of qPCR data showed a remarkable increase in the expression levels of GATA3 and TH2LCRR in the PBMCs of patients with schizophrenia compared to controls. Interestingly, both TH2LCRR and GATA3 exhibited greater diagnostic value in female subjects. However, our data showed no significant difference in the expression levels of Th1-related genes (IFNG-AS1, TBX21, IFNG) and IL-4 between diagnostic groups. Furthermore, the expression levels of IFNG-AS1 and TH2LCRR were positively correlated with cytokine expression in patient subjects. These findings further support the pivotal role of Th1/Th2 imbalance in the pathogenesis of schizophrenia. Our data highlight the necessity to evaluate the potential efficacy of immune-related genes to identify promising biomarkers for both the diagnosis and therapy of patients with schizophrenia.