Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Viale Michelangelo 41, 50125 Florence, Italy.
Department of Biomedical Sciences and Human Oncology, 1st Dermatologic Clinic, University of Turin, Via Cherasco 23, 10126 Turin, Italy.
J Dermatol Sci. 2015 Jan;77(1):54-62. doi: 10.1016/j.jdermsci.2014.11.003. Epub 2014 Nov 18.
Dermatitis herpetiformis (DH) and celiac disease (CD) are considered as autoimmune diseases that share a defined trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not fully understood and no data are available about the immune regulation in such a disease.
The aim of this study was to assess if alterations in the pattern of the immune response and, in particular, impairments of regulatory T (Tregs) cells may contribute to the phenotypic differences between DH and CD.
We investigated the presence of Tregs cell markers, in the skin, the duodenum and the blood of patients with DH by immunohistochemistry, confocal microscopy and flow cytometry. As controls, we included patients with bullous pemphigoid, patients with CD without skin lesions, as well as healthy subjects (HS).
In the skin of DH patient, we found a significantly lower proportion of FOXP3(+) Tregs and IL-10(+) cells than in HS (p < 0.001 for both cell populations). In duodenal samples, no differences where found in the proportion of Tregs between patients with DH and patients with CD without skin manifestations. Finally, the frequency of CD25(bright)FOXP3(+) cells within the CD4(+) subset was significantly reduced in CD patients either with or without DH with respect to HS (p = 0.029 and p = 0.017, respectively).
Our findings suggested that a reduction of Tregs may play a major role in the skin, leading to a defective suppressive function and thus to the development of the lesions. By contrast, no differences could be detected about Tregs between patients with DH and patients with CD in the duodenum, suggesting that the mechanisms of the intestinal damage are similar in both diseases.
疱疹样皮炎（DH）和乳糜泻（CD）被认为是自身免疫性疾病，它们具有明确的触发因素（麸质）和共同的遗传背景（HLA-DQ2/DQ8）。然而，DH 的发病机制尚不完全清楚，也没有关于这种疾病的免疫调节的数据。
本研究旨在评估免疫反应模式的改变，特别是调节性 T（Treg）细胞的功能障碍，是否有助于解释 DH 和 CD 之间的表型差异。
我们通过免疫组织化学、共聚焦显微镜和流式细胞术检测 DH 患者皮肤、十二指肠和血液中 Treg 细胞标志物的存在。作为对照，我们纳入了大疱性类天疱疮患者、无皮肤损伤的 CD 患者以及健康受试者（HS）。
在 DH 患者的皮肤中，我们发现 FOXP3+Treg 和 IL-10+细胞的比例明显低于 HS（两组细胞均为 p < 0.001）。在十二指肠样本中，DH 患者和无皮肤表现的 CD 患者之间 Treg 的比例没有差异。最后，与 HS 相比，CD 患者中 CD4+细胞亚群中 CD25（bright）FOXP3+细胞的频率显著降低（分别为 p = 0.029 和 p = 0.017）。
我们的研究结果表明，Treg 的减少可能在皮肤中起主要作用，导致其抑制功能缺陷，从而导致病变的发生。相比之下，DH 患者和 CD 患者在十二指肠中 Treg 之间没有差异，这表明两种疾病的肠道损伤机制相似。
