Itch is the most troublesome symptom in atopic dermatitis (AD). Although skin barrier dysfunctions and aberrant immune responses are thought to contribute to AD itch, the precise mechanism is yet to be clarified. In this study, we newly established a chronic AD mouse model to identify the mechanism of itch in AD. Hairless mice were fed a special diet deficient in polyunsaturated fatty acids and starch to induce dry skin with barrier dysfunction (dry-skin mice). Ointments containing a crude extract of house-dust mite were then repeatedly applied to the skin of the dry-skin mice. The dry-skin mice treated with a mite extract (DM mice) exhibited AD-like skin manifestations and histology. DM mice showed robust scratching behavior, which was partially attenuated by treatment with either betamethasone or tacrolimus, but not by that with olopatadine. Genome-wide gene expression analysis revealed that DM mice had a similar skin gene expression profile to that of human AD. Furthermore, increased expressions of Chi3l3, Chi3l4 and Ear11 in DM mice were consistent with exacerbation of scratching behavior. Thus, we will further examine the role of proteins encoded by these genes in itch-related behavior in this AD model.

To: 要旨(抄録)