Abstract
BackgroundPhoto(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.MethodsPeripheral 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.ResultsPhoto(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%).ConclusionThese 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.
Highlights
Narrowband ultraviolet B (UVB, 311 nm) phototherapy is a popular treatment for refractory lesions such as those of psoriasis, atopic dermatitis (AD), and vitiligo [1]
In our previous clinical study [8], we examined whether bath-psoralen and UVA (PUVA) affects circulating Treg in the peripheral blood of psoriasis patients; 10 healthy controls and 18 psoriasis patients who had not previously received photo(chemo)therapy were enrolled
Bath-PUVA therapy improved Psoriasis Area and Severity Index (PASI) scores and increased Foxp3+ Treg in all patients [8]. These findings indicate that bath-PUVA restores Treg in psoriasis patients, and suggest that the clinical efficacy of bath-PUVA therapy for psoriatic patients is due to the induction of Foxp3+ Treg
Summary
Narrowband ultraviolet B (UVB, 311 nm) phototherapy is a popular treatment for refractory lesions such as those of psoriasis, atopic dermatitis (AD), and vitiligo [1]. Narrowband UVB therapy and bath-PUVA therapy generally induce a relatively long remission period of approximately 4 to 6 months in patients with psoriasis, a relatively long remission period that might be due only partly to the induction of apoptosis. Bath-PUVA therapy improved Psoriasis Area and Severity Index (PASI) scores and increased Foxp3+ Treg in all patients [8]. These findings indicate that bath-PUVA restores Treg in psoriasis patients, and suggest that the clinical efficacy of bath-PUVA therapy for psoriatic patients is due to the induction of Foxp3+ Treg. It is not known, whether photo(chemo)therapy restores Treg function. We evaluated the effects of photo(chemo)therapy on the Th17/Treg balance and Treg function
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