Periostin Contributes to the Pathogenesis of Atopic Dermatitis by Inducing TSLP Production from Keratinocytes

Abstract

Background: 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. Methods: The ears of C57BL/6 mice, BALB/c mice, and Rag-2−/− γc−/− 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. Results: Epicutaneous sensitization with HDM induced AD-like phenotypes and accumulation of periostin in dermis in C57BL/6 mice but not in Rag-2−/− γc−/− mice. In vitro organotypic coculture systems revealed that periostin promoted survival and proliferation of keratinocytes and directly induced production of thymic stromal lymphopoietin (TSLP). Conclusions: Our results suggest that periostin exacerbates the pathogenesis of AD through TSLP production from keratinocytes.

Keywords

• atopic dermatitis
• house dust mite
• periostin
• Th2 cells
• TSLP