Antiga E, Quaglino P, Volpi W, Pierini I, Del Bianco E, Bianchi B, Novelli M, Savoia P, Bernengo M G, Fabbri P, Caproni M
Department of Critical Care, Section of Dermatology, University of Florence, Florence, Italy.
Department of Medical Sciences, 1 st Dermatologic Clinic, University of Turin, Turin, Italy.
J Eur Acad Dermatol Venereol. 2014 Feb;28(2):222-30. doi: 10.1111/jdv.12091. Epub 2013 Jan 18.
Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid (BP) with contrasting results.
To characterize Tregs and to determine the serum levels of regulatory cytokines in patients with BP.
In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4(+) , CD25(+) , forkhead/winged helix transcription factor (FOXP3)(+) , transforming growth factor (TGF)-β(+) and interleukin (IL)-10(+) cells. In addition, the number of CD4(+) CD25(++) FOXP3(+) Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-β and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis (AD) and healthy donors.
The frequency of FOXP3(+) cells was significantly reduced in skin lesions from patients with BP (P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10(+) cells was lower in BP than in psoriasis (P < 0.001) and AD (P = 0.002), while no differences were observed in the number of TGF-β(+) cells. CD4(+) CD25(++) FOXP3(+) Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls (P < 0.001), and augmented significantly after steroid therapy (P = 0.001). Finally, TGF-β and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy (P = 0.01).
These data suggest that the depletion of Tregs and of IL-10 in patients with BP may be an important factor in the pathogenesis of the disease.
尽管调节性T细胞（Tregs）在几种自身免疫性皮肤病中受到影响，但仅有两项针对大疱性类天疱疮（BP）患者的研究，结果却相互矛盾。
对BP患者的Tregs进行特征分析，并测定其调节性细胞因子的血清水平。
对BP患者的皮损进行免疫组织化学和共聚焦显微镜检查，检测CD4(+)、CD25(+)、叉头/翼状螺旋转录因子（FOXP3）(+)、转化生长因子（TGF）-β(+)和白细胞介素（IL）-10(+)细胞。此外，通过流式细胞术评估外周血中CD4(+) CD25(++) FOXP3(+) Tregs的数量，并在类固醇治疗前后通过酶联免疫吸附测定法测定血清样本中TGF-β和IL-10的水平。对照组包括银屑病患者、特应性皮炎（AD）患者和健康供者。
与银屑病和AD相比，BP患者皮肤病变中FOXP3(+)细胞的频率显著降低（P < 0.001）。此外，BP患者中IL-10(+)细胞的数量低于银屑病患者（P < 0.001）和AD患者（P = 0.002），而TGF-β(+)细胞的数量未观察到差异。与健康对照组相比，BP患者外周血中CD4(+) CD25(++) FOXP3(+) Treg显著减少（P < 0.001），类固醇治疗后显著增加（P = 0.001）。最后，与健康对照组相比，BP患者的TGF-β和IL-10血清水平相似。然而，治疗后，BP患者的IL-10血清水平显著高于治疗前（P = 0.01）。
这些数据表明，BP患者中Tregs和IL-10的耗竭可能是该疾病发病机制中的一个重要因素。
