Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
J Clin Invest. 2012 Jul;122(7):2590-600. doi: 10.1172/JCI58978. Epub 2012 Jun 11.
Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with αv integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or αv integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.
过敏原暴露引发的过敏炎症常导致特应性皮炎（AD）和支气管哮喘等慢性炎症性疾病的发生。过敏炎症慢性化的机制仍未解决。骨膜蛋白是一种最近被描述的细胞外基质蛋白，它与几种细胞表面整合素分子相互作用，为组织发育和重塑提供信号。在这里，我们使用皮肤炎症的小鼠模型显示，骨膜蛋白是过敏炎症放大和持续的关键介质。Th2 细胞因子 IL-4 和 IL-13 刺激成纤维细胞产生骨膜蛋白，骨膜蛋白与角质形成细胞上的功能性骨膜蛋白受体αv 整合素相互作用，诱导促炎细胞因子的产生，进而加速 Th2 型免疫反应。因此，抑制骨膜蛋白或αv 整合素可防止变应原诱导的皮肤炎症的发生或进展。因此，骨膜蛋白建立了一个恶性循环，将 Th2 型免疫反应与角质形成细胞激活联系起来，并在过敏性皮肤炎症的放大和慢性化中发挥关键作用。
