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

BACKGROUND 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. METHODS 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. RESULTS 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%). CONCLUSION 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.