FoxP3+T regulatory cells in Rheumatoid arthritis and the imbalance of the Treg/TH17 cytokine axis

AbstractAim of the workTo investigate the frequency of FoxP3+CD4+CD25+high cells (Tregs) in rheumatoid arthritis (RA) patients and their association with clinical and radiological parameters. Also to study the possible relationship between Tregs and TGF-β as an indicator of Treg function, with IL17 as an indicator of Th17 function and with the ratio between them to throw light on the imbalance between these two cytokines in RA.Patients and methodsForty RA patients and 20 age and sex matched healthy controls were enrolled in the study. Patients underwent clinical, laboratory and radiographic assessment. The frequency of Tregs was determined by flowcytometry. Serum IL-17 and TGF-β cytokines were analyzed using ELISA.ResultsThe frequency of Tregs was significantly decreased among RA patients and with a parallel significant decrease in the mean fluorescence intensity (MFI) of FoxP3. Both IL-17 and TGFβ were significantly increased. Tregs, IL-17 and TGF-β did not correlate with any of the clinical findings, laboratory and radiographic scores. TGFβ:IL-17 ratio dropped from 15.8±9.6 among controls to 5.33±5 among patients with mild-to-moderate activity and 2.45±1.8 among patients with severe activity.ConclusionRA patients show a decreased frequency of Tregs that is not associated with clinical parameters or radiological damage. The five-fold increase in IL-17 and two-fold increase in TGF-β prove a disturbance in the balance of the cytokine milieu in favor of inflammation and draw attention to the importance of considering the interplay of the Treg/TH17 cytokine axis in the pathogenesis of RA; hence aiming at restoring that balance during treatment