Decreased mRNA expression level of FOXP3 correlate with TNF-α in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis patients: a case control study

Abstract

Background:Forkhead box P3 (FOXP3), a transcription factor is thought to be the master regulator of regulatory T (Treg) cells in maintaining peripheral tolerance and autoimmunity. The number and functional capabilities have been reported to be low in several diseases including RA, which affects the immune regulatory action of Treg cells. Proinflammatory cytokines such as tumor necrosis factor α (TNF-α), are important in RA pathogenesis, but the influence on Treg cells is poorly understood. Methods:In the present study, the messenger RNA (mRNA) expressions of FOXP3 and TNF-α in a group of patients with RA (N = 23) and a healthy control group (N = 17) were studied in peripheral blood mononuclear cells (PBMCs). PBMCs were chosen as they are practical samples in which changes caused by disease or therapy can be conveniently monitored. Results:Expression of FOXP3 was lower (P < 0.0001, 0.76 folds) and TNFα gene expression was higher (P < 0.0001, 2.28 folds) in RA patients when compared with the healthy control group. However, a statistically significant correlation could not be established between the FOXP3 and disease activity, but relative mRNA expression of FOXP3 and TNF-α showed a statistically significant correlation (P < 0.0283) in RA patients when compared with the healthy control group. Conclusions:The results suggested that decreased expression of FOXP3 gene and increased level of TNF-α expression in the presence of rheumatoid factor antibodies (RF) may impair the activity of Treg cells with higher TNF-α levels when compared with patients who were negative for RF.