The Role of Cytokines/Chemokines in the Pathogenesis of Atopic Dermatitis
The Role of Cytokines/Chemokines in the Pathogenesis of Atopic Dermatitis
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DOI：
10.1159/000323299
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Mizutani, Hitoshi
中科院分区：
文献类型：
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作者：
Yamanaka, Kei-ichi;Mizutani, Hitoshi
特应性皮炎（AD）是最常见和最易复发的皮肤过敏性疾病。AD的特征在于与皮肤中细胞浸润增加、IgE和嗜酸性粒细胞增多的循环水平升高相关的Th 2型细胞因子的主要表达。这些发现与CD 4 + T细胞中白细胞介素（IL）-4和IL-13的表达呈正相关。在AD患者中，Th 2细胞、嗜酸性粒细胞、肥大细胞和树突状细胞在皮损中显著增加。然而，Th 1细胞也参与AD病变的发展。事实上，包括γ-干扰素和IL-12在内的Th 1细胞因子mRNA表达在慢性病变中升高，以及在急性AD病变中升高的Th 2细胞因子。Th 17谱系和调节性T（T-reg）细胞的发现将简单的Th-1/Th-2平衡概念转变为4向平衡系统。Th 17/22细胞、Foxp 3 +T-reg和产生IL-10的T细胞（Tr 1）参与局部和全身免疫环境的机制。此外，在高IL-18环境中，由Th 1细胞排列的超级Th 1细胞也参与小鼠AD病变的发展。通过Th 1诱导剂校正Th 2细胞因子优势在实验模型中显示出有效性。然而，精细调节Th 1、Th 2、Th 17/22和T-reg细胞之间微妙的4向平衡对于控制AD是必需的。一些生物制剂在AD中的疗效已有报道。然而，需要进一步的研究，使生物制剂，抗原特异性免疫治疗，非抗原特异性免疫治疗，拮抗剂和生物反应调节剂在临床上的治疗应用成为可能。这些新的方法可能构成一个潜在的治愈性治疗AD。版权所有（C）2011 S. Karger AG，巴塞尔
Atopic dermatitis (AD) is the most common and relapsing allergic disease of the skin. AD is characterized by a predominant expression of Th2-type cytokines associated with increased cellular infiltration in the skin, elevated circulating levels of IgE and eosinophilia. These findings are positively correlated with interleukin (IL)-4 and IL-13 expression in CD4+ T cells. In AD patients, Th2 cells, eosinophils, mast cells and dendritic cells are markedly increased in the skin lesions. However, Th1 cells are also involved in the development of AD lesions. In fact, Th1 cytokine mRNA expressions including gamma-interferon and IL-12 are elevated in the chronic lesions as well as elevated Th2 cytokines in the acute AD lesions. The discovery of Th17 lineage and regulatory T (T-reg) cells shifted the simple Th-1/Th-2 balance concept into a 4-way balance system. Th17/22 cells, Foxp3+T-reg and IL-10-producing T cells (Tr1) are involved in the mechanism of a local and systemic immunological milieu. In addition, super Th1 cells arranged from Th1 cells in high IL-18 milieu are also involved in the development of mouse AD lesions. Correction of Th2 cytokine predominance by Th1 inducers shows effectiveness in experimental models. However, fine-tuning of the delicate 4-way balance among Th1, Th2, Th17/22 and T-reg cells is required for the control of AD. Efficacy of some biological agents in AD has been reported. However, further investigations are required to make possible the therapeutic application of biologicals, antigen-specific immunotherapy, non-antigen-specific immunotherapy, antagonists and biological response modifiers in the clinic. These novel approaches may constitute a potential curative therapy for AD. Copyright (C) 2011 S. Karger AG, Basel