Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Japan.
Allergol Int. 2012 Dec;61(4):563-72. doi: 10.2332/allergolint.10-OA-0297. Epub 2012 Aug 25.
Atopic dermatitis (AD) is a chronic inflammatory skin disease where Th2-type immune responses are dominant. Keratinocytes persistently secrete proinflammatory cytokines and chemokines, amplifying Th2-type responses in AD. We have recently reported that periostin, an extracellular matrix protein induced by Th2 cytokines, plays a critical role in AD. In the present study, we have further investigated the characteristics of our allergen-induced AD model mice and the role of periostin in the pathogenesis of AD.
The ears of C57BL/6 mice, BALB/c mice, and Rag-2-/- γ(c)-/- mice (BALB/c background) were epicutaneously sensitized repeatedly with HDM. Mice were analyzed after the final sensitization. To examine the direct role of periostin, we reconstituted skin in vitro by coculture of keratinocytes with wild-type or periostin-deficient fibroblasts.
Epicutaneous sensitization with HDM induced AD-like phenotypes and accumulation of periostin in dermis in C57BL/6 mice but not in Rag-2-/- γ(c)-/- mice. In vitro organotypic coculture systems revealed that periostin promoted survival and proliferation of keratinocytes and directly induced production of thymic stromal lymphopoietin (TSLP).
Our results suggest that periostin exacerbates the pathogenesis of AD through TSLP production from keratinocytes.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其中 Th2 型免疫反应占主导地位。角质形成细胞持续分泌促炎细胞因子和趋化因子，放大 AD 中的 Th2 型反应。我们最近报道，由 Th2 细胞因子诱导的细胞外基质蛋白骨桥蛋白在 AD 中发挥关键作用。在本研究中，我们进一步研究了我们的变应原诱导 AD 模型小鼠的特征以及骨桥蛋白在 AD 发病机制中的作用。
C57BL/6 小鼠、BALB/c 小鼠和 Rag-2-/-γ(c)-/-小鼠（BALB/c 背景）的耳朵通过表皮致敏反复用 HDM 致敏。最后一次致敏后分析小鼠。为了研究骨桥蛋白的直接作用，我们通过角质形成细胞与野生型或骨桥蛋白缺陷型成纤维细胞的共培养来体外重建皮肤。
HDM 的表皮致敏在 C57BL/6 小鼠中诱导出类似于 AD 的表型，并在真皮中积累骨桥蛋白，但在 Rag-2-/-γ(c)-/-小鼠中则没有。体外器官型共培养系统显示，骨桥蛋白促进角质形成细胞的存活和增殖，并直接诱导胸腺基质淋巴细胞生成素（TSLP）的产生。
我们的结果表明，骨桥蛋白通过角质形成细胞产生 TSLP 加剧 AD 的发病机制。
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