title: Down-regulation of the Th1, Th17, and Th22 pathways due to anti-TNF-α treatment in psoriasis.
abstract: BACKGROUND
  Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis.
  
  
  OBJECTIVE
  To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response.
  
  
  METHODS
  This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α).
  
  
  RESULTS
  At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines.
  
  
  CONCLUSIONS
  The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis.
authors.affiliation: Department of Dermatology and Venereology, The Affiliated Zhongshan Hospital of DaLian University, 116001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Luan
authors.affiliation: Department of Dermatology and Venereology, 1st Affiliated Hospital of DaLian Medical University, 116011, China.
authors.forename: Shixin
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Dermatology and Venereology, 1st Affiliated Hospital of DaLian Medical University, 116011, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Venereology, 1st Affiliated Hospital of DaLian Medical University, 116011, China; Department of Dermatology and Venereology, Shenzhen Hospital of Hong Kong University, 518053, China. Electronic address: lxmdl_1956@126.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22
keywords: Adalimumab; Anti-tnfα; Psoriasis; Th1 cell; Th17 cell; Th22 cell