J Clin Invest.:Periostin介导慢性过敏性炎症疾病

6月11日，J Clin Invest.杂志在线报道了Periostin(一种细胞基质蛋白)在慢性过敏性炎症疾病中发挥的重要作用。由接触过敏原引发的过敏性炎症常导致慢性炎症性疾病，如遗传性过敏症皮炎（AD）和支气管哮喘的发病。慢性过敏性炎症的机制仍然没有得到解决。

Periostin是最近发现的一种细胞基质蛋白，在人类由POSTN基因编码，作为配体与alpha-V/beta-3和alpha-V/beta-5整合素相互作用，支持上皮细胞的粘附和迁移的蛋白质。它与几个细胞表面的整合素分子相互作用，为组织发展和重构提供信息。利用皮肤炎症小鼠模型，研究者发现，periostin是放大和维持过敏性炎症的一个关键的介导因子。 Th2(辅助性T细胞2型)细胞因子IL-4（白介素-4）和IL-13（白介素-13）刺激成纤维细胞产生periostin。Periostin与其在角化细胞上的受体αV整合素相互作用，诱导炎性细胞因子的生产，从而加快了Th2型免疫反应。

因此，抑制periostin或αV整合素阻止过敏引起的皮肤炎症的发生或进展。由此，periostin启动了一个恶性循环，将角化细胞活化与Th2型免疫反应联系在一起，并且在放大和慢性化过敏性皮肤炎过程中发挥关键作用。

该研究，为深入理解慢性过敏性炎症疾病提供了新的启示，并为治疗找到了潜在的靶点。

doi:10.1016/j.cell.2011.10.017
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Periostin promotes chronic allergic inflammation in response to Th2 cytokines

Miho Masuoka1, Hiroshi Shiraishi1, Shoichiro Ohta2, Shoichi Suzuki1, Kazuhiko Arima1, Shigehisa Aoki3, Shuji Toda3, Naoki Inagaki4, Yuichi Kurihara5, Sayaka Hayashida5, Satoshi Takeuchi5, Kenta Koike6, Junya Ono7, Hirokazu Noshiro6, Masutaka Furue5, Simon J. Conway8, Yutaka Narisawa9 and Kenji Izuhara1,2

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.