Clarification of the functional roles of matrix proteins in the pathogenesis of allergic inflammation

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It is well known that type 2 immunity is important for allergicinflammation. To examine how IL-4 or IL-13, signature type 2 cytokines, contributes to the pathogenesis of allergic inflammation, we in this study analyzed functions of periostin,an extracellular matrix protein induced by IL-4 or IL-13. We found that periostin playsan important role for the chronicity of allergic inflammation in atopic dermatitis. IL-4 or IL-13 induces periostin production in fibroblasts. Periostin induces TSLP production in keratinocytes by binding to integrin molecules on their cell surface. Then TSLP induces Th2 differentiation in naive T cells. Thus, the vicious cycle composed of IL-4/IL-13, periostin, integrin, and TSLP is important for the pathogenesisof atopic dermatitis. The finding that the neutralizing antibodies against av integrin inhibited dermatitis suggests that periostin can be a therapeutic target against atopic dermatitis. We also found that periostin is involved in the pathogenesis of variousinflammatory diseases such as pulmonary fibrosis, scleroderma, gallbladder carcinoma,IgG4-related sclerosing sialadenitis, eosinophilic otitis media, allergic rhinitis and chronic rhinosinusitis, and proliferative diabetic retinopathy. Furthermore, we found that periostin plays an important role in wound repair, which is a physiological function of periostin. The underlying mechanism of the chronicity of allergic inflammationby periostin is the first example showing some host factor is involved in it. It is hopedthat development of inhibitors targeting periostin will lead to development of therapeutic agents against atopic dermatitis having a novel mechanism.