Li Luan1, Shixin Han2, Hua Wang2, Xiaoming Liu3. 1. Department of Dermatology and Venereology, The Affiliated Zhongshan Hospital of DaLian University, 116001, China. 2. Department of Dermatology and Venereology, 1st Affiliated Hospital of DaLian Medical University, 116011, China. 3. 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.
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. CONCLUSION: The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis.
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 psoriasispatients 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 psoriasispatients 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. CONCLUSION: 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: F D'Amico; M Granata; E Skarmoutsou; C Trovato; G Lovero; P Gangemi; V Longo; M Pettinato; M C Mazzarino Journal: Inflamm Res Date: 2018-03-31 Impact factor: 4.575
Authors: Sandro C Furiati; Jonatas S Catarino; Marcos V Silva; Rafaela F Silva; Rayane B Estevam; Reginaldo B Teodoro; Sanivia L Pereira; Meire Ataide; Virmondes Rodrigues; Denise B R Rodrigues Journal: Sci Rep Date: 2019-05-17 Impact factor: 4.379
Authors: Richard B Warren; Nick J Reynolds; Christopher E M Griffiths; Jonathan N Barker; Catherine H Smith; Rosa Andres-Ejarque; Hira Bahadur Ale; Katarzyna Grys; Isabella Tosi; Shane Solanky; Chrysanthi Ainali; Zeynep Catak; Hemawtee Sreeneebus; Jake Saklatvala; Nick Dand; Emanuele de Rinaldis; Anna Chapman; Frank O Nestle; Michael R Barnes; Paola Di Meglio Journal: Nat Commun Date: 2021-08-06 Impact factor: 14.919