Photo(chemo)therapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis.
Photo(chemo)therapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis.
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DOI：
10.1371/journal.pone.0054895
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Morita A
中科院分区：
文献类型：
--
作者：
Furuhashi T;Saito C;Torii K;Nishida E;Yamazaki S;Morita A
光（化）疗广泛用于治疗银屑病，其发病机制可能是由Th 17细胞/调节性T细胞（Treg）失衡引起的。在本研究中，我们评估了光（化疗）治疗对Th 17/Treg平衡和Treg功能的影响。外周血取自用长波紫外线A（UVA，n = 50）或窄带紫外线B（UVB，n = 18）治疗的银屑病患者和年龄匹配的健康志愿者（n = 20）。 分析CD 3 + CD 4 +IL-17 A+或CD 4 + CD 25 + Foxp 3+细胞，以通过荧光激活细胞分选估计Th 17或Treg数量。此外，将来自接受PUVA治疗的患者（n = 14）的CD 4 + CD 25 − T细胞在CFSE中孵育，并在有或没有CD 4 + CD 25 +T细胞的情况下活化，并分析CD 4 + CD 25 +T细胞的抑制功能。 在Th 17升高的患者中，光（化疗）疗法显著地将Th 17水平从5.66±3.15%降低至2.96±2.89%（Th 17/CD 4>3.01% [对照组的平均值+SD]）。相比之下，光（化疗）疗法使Treg水平低于4.07%（定义为对照组的平均值）的患者的Treg水平从2.77±0.75显著增加至3.40±1.88%。此外，虽然Treg在对照组（Treg功能比率94.4±4.28%）中抑制CD 4 + CD 25 − T细胞增殖的程度高于患者（70.3±25.1%），但PUVA将Treg功能比率显著增加至88.1± 6.47%。与对照组相比，重症患者（>30 PASI）中的Th 17水平显著更高。未达到PASI 50的患者治疗后Th 17水平（3.78±4.18%）显著高于达到PASI 75的患者（1.83±1.87%）。达到PASI 90的患者Treg水平（4.89±1.70%）显著高于未达到PASI 90的患者（3.90±1.66%）。治疗前Th 17高降低组Treg水平（5.16±2.20%）显著高于Th 17高升高组（3.33±1.39%）。这些发现表明Treg在银屑病患者中功能失调，而光化学疗法恢复了那些功能失调的Treg。光（化疗）治疗解决了银屑病患者的Th 17/Treg失衡。
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.
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DOI：
10.1038/jid.2010.166
发表时间：
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期刊：
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影响因子：
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2008-02-01
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