A role for thymic stromal lymphopoietin (TSLP) in atopic dermatitis (AD) has recently been postulated. In in vitro studies, TSLP was shown to activate CD11c+ dendritic cells, which were subsequently able to tolerize naive CD4+ T cells towards a pro-allergic inflammatory profile. In addition, biopsies of AD lesions were found to express high levels of TSLP. These data support a key early role for TSLP in the pathogenesis of Th2-mediated allergic disease including AD. However, further work needs to be done to define more precisely its role in allergic disease and also to determine how it is regulated. The present research proposal has two aims. The first is to characterize a proposed animal model of AD. We have already developed transgenic mice with skin-specific TSLP overexpression, which demonstrate all of the characteristic findings of AD. We now propose to characterize the cell types and mediators involved in the skin inflammation observed in these mice and to define the pathogenetic role of TSLP in vivo in order to further establish these mice as a useful model of human disease.
The second aim i s to characterize the cis-regulatory elements that control expression of TSLP.
