Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopicdermatitis-like lesions

We have examined the expression of chemokines and their receptors in the at opic dermatitis-like (AD-like) lesions of NC/Nga mice. Such lesions develop when the mice are kept in conventional conditions, but not when they are k ept isolated from specific pathogens. The thymus- and activation-regulated chemokine TARC is unexpectedly highly expressed in the basal epidermis of 1 4-week-old mice with lesions, whereas it is not expressed in the skin witho ut lesions. Production of TARC by keratinocytes was confirmed by culturing murine keratinocytic cell line cells (PAM212) with TNF-alpha, IFN-gamma, or IL-1 beta. Expression of another Th2 chemokine, macrophage-derived chemoki ne (MDC), was observed in the skin from mice kept in both conventional and pathogen-free conditions, but expression of MDC was increased severalfold i n the skin with lesions. The cellular origin of MDC was identified to be de rmal dendritic cells. Infiltration of the skin by IL-4-producing T cells an d mast cells, and the increase of CCR4 mRNA in the skin, coincided with the development of AD lesions. These observations indicate that TARC and MDC a ctively participate in the pathogenesis of AD-like lesions in NC/Nga mice a nd that these Th2 chemokines could be novel targets for intervention therap y of AD in humans.