Periostin promotes chronic allergic inflammation in response to Th2 cytokines

Masuoka M., et al. J Clin Invest. 2012; 122(7):2590–2600.

Speaker：Yu-Pu Hsia (夏雨璞)                   )                                     Time：15:10~16:00, October 24, 2012

Commentator: Dr. Yee-Shin Lin (林以行老師)      )               Place：Room 601

Abstract:

      Atopic dermatitis (AD) is an allergic inflammatory disease caused by the interaction between skin barrier damage and allergic skin inflammation. It is a Th2-type dominant inflammation. Previous study indicated that activation of keratinocytes produce thymic stromal lymphopoietin (TSLP) to induce Th2-type responses in AD [1]. However, mechanism of allergic inflammation is not clear. In this study, AD model is induced by epicutaneous sensitization with house dust mite extract (HDM). Authors found that periostin, a matricellular protein belonging to extracellular matrix (ECM) proteins, was involved in this skin inflammation. Periostin is important in development of tissue. Recent study indicated that periostin has another role in cutaneous wound repair [2]. First, the author demonstrated Postn^-/- mice appeared normal skin even in HDM-sensitization and down regulation of Th-2 type responses. Then they reconstituted skin tissues in vitro with 3-dimensional organotypic co-culture system using keratinocytes and fibroblasts. They confirmed that IL-13 stimulated fibroblasts to produce periostin enhancing proliferation and differentiation of keratinocytes then induced TSLP production. It is Th2 type immune response via activation of dendritic cells. Furthermore, periostin induced TSLP production though the NF-κB pathway. Periostin binds to integrin molecules but only α_νβ₃ was expressed predominantly in the dermis. Therefore, skin inflammation was reduced in HDM-sensitized mice by blocking α_ν with neutralizing antibody. Actually, AD patients highly express periostin in skin tissue providing a strong evidence for involvement of periostin in AD pathogenesis. In conclusion, periostin plays a critical role in the amplification and maintaining of allergic skin inflammation by linking Th2-type inflammatory responses and keratinocytes activation.

References:

1.Jariwala S. P., et al. The role of thymic stromal lymphopoietin in the

1. immunopathogenesis of atopic dermatitis. Clin Exp Allergy.2011; 41(11):1515-20.

1.2.     Ontsuka K, et al. Periostin, a matricellular protein, accelerates cutaneous wound repair

1.by activating dermal fibroblasts. Exp Dermatol. 2012; 21(5):331–336.