Th1, Th2, Th17 and Regulatory T Cell Pattern in Psoriatic Patients: Modulation of Cytokines and Gene Targets Induced by Etanercept Treatment and Correlation with Clinical Response

Background: Psoriasis is sustained by pro-inflammatory CD4+ T helper cells mainly belonging to the Th1, Th17 and Th22 lineage. Objective: To identify whether treatment with the anti-tumour-necrosis-factor antagonist etanercept is able to induce significant modulations in transcription factor and cytokine mRNA gene expressions related to the different T cell immune response polarization (Th1, Th2, Th17 and regulatory T cells, T-reg) and to correlate them with clinical response. Methods: The study population included 19 psoriasis patients treated with etanercept and 19 healthy subjects. Blood samples were collected at baseline and every 4 weeks during treatment. Taqman quantitative real-time polymerase chain reaction was applied to analyse the expression of: Stat-4, T-bet, IL-12p35 and IFN-gamma (Th1-related); GATA-3, IL-4 (Th2-related); Stat-3, ROR gamma t, IL-23p19 (Th17-related); Foxp3, IL-2 (T-reg-related). Flow cytometry was applied to analyse CD4+ CD25+(bright)Foxp3+ cells in peripheral blood. Results: Upregulation of Th1 and Th17 and downregulation of T-reg subsets was found at baseline. The response to etanercept could be associated with a significant reversal of the Th1/Th17 activation, and a concomitant upregulation of Th2 and T-reg subsets. Conclusion: Our data may contribute to a better understanding of the mechanisms underlying the achievement of clinical response in psoriasis and could be helpful for the identification of early predictive markers of response. Copyright (C) 2011 S. Karger AG, Basel