State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Xianlin Avenue 163, Nanjing, 210023, Jiangsu, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Xianlin Avenue 163, Nanjing, 210023, Jiangsu, China; Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing University, Hankou Road 22, Nanjing, 210093, Jiangsu, China.
Mol Immunol. 2021 Feb;130:104-112. doi: 10.1016/j.molimm.2020.11.013. Epub 2020 Dec 11.
Atopic dermatitis is a severe, chronic relapsing inflammatory disease of the skin with family clustering. It is characterized into acute phase, which is dominated by T helper 2-type immune responses, and chronic phase, which is dominated by T helper 1-type immune responses. Studies have shown that 3,3'-diindolylmethane not only has antitumor effects but also can relieve symptoms of inflammatory diseases by inhibiting the nuclear factor-κB signaling pathway and regulating T cell differentiation. To study the effect of 3,3'-diindolylmethane on atopic dermatitis and the underlying mechanism, a mouse model of acute atopic dermatitis was established using 2,4-dinitrofluorobenzene. After intraperitoneal injection of 3,3'-diindolylmethane, skin erythema and edema in mice were significantly alleviated. Furthermore, 3,3'-diindolylmethane reduced immune activation, probably by inhibiting the secretion of thymic stromal lymphopoietin by keratinocytes. 3,3'-Diindolylmethane also promoted the differentiation of regulatory T cells and inhibited the activation of T helper 2 and T helper 17 cells to reduce atopic dermatitis-related immune responses. However, it showed no significant effect on the differentiation of T helper 1 cells. These results indicate that 3,3'-diindolylmethane has a significant inhibitory effect on T helper 2 cells in the acute phase of atopic dermatitis. Our findings may provide not only more insights into the pathological mechanism of AD, but also a new candidate medicine for it.
特应性皮炎是一种具有家族聚集性的严重、慢性复发性皮肤炎症。它分为急性期，以辅助性 T 细胞 2 型免疫反应为主，和慢性期，以辅助性 T 细胞 1 型免疫反应为主。研究表明，二吲哚甲烷不仅具有抗肿瘤作用，还可以通过抑制核因子-κB 信号通路和调节 T 细胞分化来缓解炎症性疾病的症状。为了研究二吲哚甲烷对特应性皮炎的作用及其潜在机制，我们使用 2,4-二硝基氟苯建立了急性特应性皮炎小鼠模型。腹腔注射二吲哚甲烷后，小鼠皮肤红斑和水肿明显减轻。此外，二吲哚甲烷减少了免疫激活，可能是通过抑制角质形成细胞分泌胸腺基质淋巴细胞生成素。二吲哚甲烷还促进了调节性 T 细胞的分化，并抑制了辅助性 T 细胞 2 和辅助性 T 细胞 17 的激活，从而减轻了特应性皮炎相关的免疫反应。然而，它对辅助性 T 细胞 1 的分化没有显著影响。这些结果表明，二吲哚甲烷对特应性皮炎急性期的辅助性 T 细胞 2 具有显著的抑制作用。我们的研究结果不仅为 AD 的病理机制提供了更深入的认识，还为其提供了一种新的候选药物。
