Institute of Medical Microbiology and Immunology, Aarhus University, Aarhus C, Denmark.
J Invest Dermatol. 2011 Jan;131(1):150-7. doi: 10.1038/jid.2010.277. Epub 2010 Sep 23.
Atopic dermatitis (AD) is a common skin disease associated with a T(H)2 response and increased levels of T(H)2-associated cytokines and IgE. The mechanisms resulting in skewing the immune response in a T(H)2 direction in AD are not fully elucidated. However, such skewing has recently been associated with IL-25 in a murine model for allergic airway disease. The aim of this study was to investigate whether IL-25 may have a role in AD. We have identified IL-25-producing cells within the dermis of AD patients and propose that these cells are dendritic cells (DCs). This is supported by in vitro experiments that indicate that monocyte-derived DCs are capable of producing IL-25. As null mutations of filaggrin are associated with the development of an impaired skin barrier in AD, we investigated whether IL-25 affects filaggrin synthesis by keratinocytes. Using mRNA analysis, we have shown that IL-25 stimulation does indeed decrease filaggrin synthesis in cultured keratinocytes. These results suggest that IL-25 produced by DCs could have a dual role as both an inducer of the T(H)2 response and as an inhibitor of filaggrin synthesis, thereby directly affecting skin barrier function in AD patients.
特应性皮炎（AD）是一种常见的皮肤疾病，与 T(H)2 反应和增加的 T(H)2 相关细胞因子和 IgE 水平有关。导致 AD 中 T(H)2 方向免疫反应倾斜的机制尚未完全阐明。然而，最近在过敏性气道疾病的小鼠模型中，这种倾斜与 IL-25 有关。本研究旨在探讨 IL-25 是否可能在 AD 中发挥作用。我们已经在 AD 患者的真皮中鉴定出产生 IL-25 的细胞，并提出这些细胞是树突状细胞（DC）。这得到了体外实验的支持，表明单核细胞衍生的 DC 能够产生 IL-25。由于丝聚蛋白的缺失突变与 AD 中皮肤屏障受损的发展有关，我们研究了 IL-25 是否会影响角质形成细胞中的丝聚蛋白合成。通过 mRNA 分析，我们已经表明，IL-25 刺激确实会降低培养角质形成细胞中的丝聚蛋白合成。这些结果表明，DC 产生的 IL-25 可以作为 T(H)2 反应的诱导剂和丝聚蛋白合成的抑制剂发挥双重作用，从而直接影响 AD 患者的皮肤屏障功能。
