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

• Published in: Dermatology (Basel) Vol. 223; no. 1; pp. 57 - 67
• Main Authors: Quaglino, P., Bergallo, M., Ponti, R., Barberio, E., Cicchelli, S., Buffa, E., Comessatti, A., Costa, C., Terlizzi, M.E., Astegiano, S., Novelli, M., Cavallo, R., Bernengo, M.G.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.10.2011; S. Karger AG
• Subjects: Adult; Biological and medical sciences; Case-Control Studies; CD4 antigen; Cytokines; Cytokines - genetics; Dermatology; Drug therapy; Etanercept; Female; Gene expression; Gene Expression Profiling; Humans; Immune system; Immunoglobulin G - therapeutic use; Immunologic Factors - therapeutic use; Lymphocytes; Male; Medical sciences; Middle Aged; Original Paper; Psoriasis; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis. Parapsoriasis. Lichen; Receptors, Tumor Necrosis Factor - therapeutic use; RNA, Messenger - metabolism; T-Lymphocytes, Regulatory - metabolism; Th1 Cells - metabolism; Th17 Cells - metabolism; Th2 Cells - metabolism; Transcription Factors - metabolism; Treatment Outcome; Transcription factors; Cytokines; Psoriasis; Etanercept; Gene expression; Regulatory T cells; Human; Skin disease; Dermatology; Antipsoriatic agent; Cytokine; Th1 lymphocyte; Immunomodulator; Treatment; Immunological investigation; T-Lymphocyte; Th2 lymphocyte; Transcription factor
• ISSN: 1018-8665; 1421-9832; 1421-9832
• DOI: 10.1159/000330330

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-γ (Th1-related); GATA-3, IL-4 (Th2-related); Stat-3, RORγt, 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.