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

Dermatology. 2011;223(1):57-67. doi: 10.1159/000330330. Epub 2011 Aug 25.

Abstract

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, Treg 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 (Treg-related). Flow cytometry was applied to analyse CD4+CD25+(bright)Foxp3+ cells in peripheral blood.

Results: Upregulation of Th1 and Th17 and downregulation of Treg 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 Treg 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytokines / genetics
  • Etanercept
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • T-Lymphocytes, Regulatory / metabolism*
  • Th1 Cells / metabolism*
  • Th17 Cells / metabolism*
  • Th2 Cells / metabolism*
  • Transcription Factors / metabolism
  • Treatment Outcome

Substances

  • Cytokines
  • Immunoglobulin G
  • Immunologic Factors
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Transcription Factors
  • Etanercept