Journal Article

Photo(chemo)therapy Reduces Circulating Th17 Cells and Restores Circulating Regulatory T Cells in Psoriasis

Yamazaki, Sayuri, Saito, Chiyo, Nishida, Emi, Furuhashi, Takuya, Morita, Akimichi, Torii, Kan

2013

Overview

Photo(chemo)therapy is widely used to treat psoriasis, the pathogenesis of which might be caused by an imbalance of Th17 cells/regulatory T cells (Treg). In the present study, we evaluated the effects of photo(chemo)therapy on the Th17/Treg balance and Treg function. Peripheral blood was obtained from psoriasis patients treated with bath-psoralen ultraviolet A (UVA, n = 50) or narrowband ultraviolet B (UVB, n = 18), and age-matched healthy volunteers (n = 20). CD3(+)CD4(+)IL-17A(+) or CD4(+)CD25(+)Foxp3(+)cells were analyzed to estimate Th17 or Treg number by fluorescence-activated cell sorting. Moreover, CD4(+) CD25(-) T cells from patients treated with PUVA(n = 14) were incubated in CFSE and activated with or without CD4(+) CD25(+)T cells, and the suppressive function of CD4(+) CD25(+)T cells were analyzed. Photo(chemo)therapy significantly reduced Th17 levels from 5.66 ± 3.15% to 2.96 ± 2.89% in patients with increased Th17 (Th17/CD4>3.01% [mean+SD of controls]). In contrast, photo(chemo)therapy significantly increased Treg levels from 2.77 ± 0.75 to 3.40 ± 1.88% in patients with less than 4.07% Treg level, defined as the mean of controls. Furthermore, while Treg suppressed the CD4(+)CD25(-) T cell proliferation to a greater extent in controls (Treg Functional Ratio 94.4 ± 4.28%) than in patients (70.3±25.1%), PUVA significantly increased Treg Functional Ratio to 88.1 ± 6.47%. Th17 levels in severe patients (>30 PASI) were significantly higher as compared to controls. Th17 levels that were left after treatment in the patients not achieving PASI 50 (3.78 ± 4.18%) were significantly higher than those in the patients achieving PASI 75 (1.83±1.87%). Treg levels in patients achieving PASI 90 (4.89 ± 1.70%) were significantly higher than those in the patients not achieving PASI 90 (3.90 ± 1.66%). Treg levels prior to treatment with Th17 high decreased group (5.16 ± 2.20%) was significantly higher than that with Th17 high increased group (3.33 ± 1.39%). These findings indicate that Treg is dysfunctional in psoriasis patients, and photochemotherapy restores those dysfunctional Treg. Photo(chemo)therapy resolved the Th17/Treg imbalance in patients with psoriasis.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Aged, 80 and over / Antigens, CD - immunology / Apoptosis / Baths / Biology / Case-Control Studies / CD25 antigen / CD3 antigen / CD4 antigen / Cell Proliferation / Chemotherapy / Cytokines / Dermatology / Disease / Female / Ficusin - pharmacology / Flow Cytometry / Fluorescence / Foxp3 protein / Geriatrics / Helper cells / Humans / Immunophenotyping / Immunoregulation / Light therapy / Lymphocytes / Lymphocytes T / Male / Medicine / Middle Aged / Narrowband / Pathogenesis / Patients / Peripheral blood / Photochemotherapy / Photodynamic therapy / Photosensitizing Agents - pharmacology / Psoralen / Psoriasis / Psoriasis - drug therapy / Psoriasis - immunology / Psoriasis - pathology / Severity of Illness Index / Skin diseases / T cell receptors / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / T-Lymphocytes, Regulatory - pathology / Th17 Cells - drug effects / Th17 Cells - immunology / Th17 Cells - pathology / Trends / Ultraviolet Rays / University graduates