A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

Deregulation of transforming growth factor-beta (TGF beta) signaling has been reported in human psoriasis. Our recent study using a keratin 5 promoter (K5.TGF beta 1(wt)) showed that transgenic mice expressing wild-type TGF beta 1 in the epidermis developed severe skin inflammation. Additional experimental data further support a direct role for TGF beta 1 overexpression in skin inflammation. First, we temporally induced TGF beta 1(wt) expression in keratinocytes in our gene-switch TGF beta 1(wt) transgenic mice and found inflammation severity correlated with TGF beta 1(wt) transgene expression. Second, deletion of T cells in K5.TGF beta 1(wt) mice significantly delayed skin inflammation and associated epidermal hyperplasia/hyperkeratosis. Third, therapeutic approaches effective for human psoriasis, that is, Etanercept and Rosiglitazone, are effective in alleviating the symptoms observed in K5. TGF beta 1(wt) mice. Future studies will analyze specific mechanisms and identify key factors in TGF beta 1-induced skin inflammation. Our mouse models will provide a useful tool for understanding the molecular mechanisms of inflammatory skin disorders in which TGF beta 1 is overexpressed.