Etanercept inhibits the TNF-α driven shifting of Th17 towards non-classic Th1 phenotype in juvenile idiopathic arthritis.

Objective. To evaluate the effects of etanercept on the phenotype of CD4+ T helper (Th) lymphocytes from patients with juvenile idiopathic arthritis (JIA) Methods. We compared the proportions of different Th subsets in peripheral blood (PB) of etanercept-treated and untreated JIA patients. An in vitro study was then performed on PB mononuclear cells (MNC) of 15 untreated JIA children by evaluating their proliferative response, as well as, their cytokine production profile, to different stimuli in presence or absence of etanercept. Results. We found lower proportions of CD4+CD161+ (non-classic) Th1 lymphocytes in PB of patients treated with etanercept than in untreated ones. In vitro, etanercept inhibited the proliferative response induced by either polyclonal or recall antigens stimulation of PBMNC. Moreover, etanercept increased in vitro the CD4+CD161+ Th17/Th1 and Th17, while decreased the non-classic Th1, subsets proportions, leaving the CD4+CD161- (classic) Th1 cells unaffected. We also found that TNF-α was able to induce in vitro the transition of Th17 lymphocytes towards the non-classic Th1 phenotype, probably thanks to the high expression of TNFRII observed in Th17 cells. Conclusion. Since we have previously demonstrated the occurrence of a shifting of CD4+CD161+ Th17 cells to the non-classic Th1 phenotype in JIA children, the present findings suggest that etanercept can also exert its disease modifying action by interfering with such a shifting.