CD8 + regulatory T cells appear impaired in number and/or function in some autoimmune diseases. However, the role of CD8 + regulatory T cells in the pathogenesis of skin inflammation and psoriasis remains unknown. In this study, we set out to analyze the capability of CD8 + regulatory T cells to inhibit skin inflammation in a murine model and to determine the frequency of CD8 + regulatory T cells in patients with psoriasis. We demonstrate that murine fully competent CD8 + regulatory T cells can be induced by stimulating naïve CD8 + T cells in the presence of TGF-β and retinoic acid (RA). Importantly, in vitro induced CD8 + regulatory T cells significantly suppressed skin inflammation in vivo. Furthermore, we found that the frequency of regulatory CD8 +CD25 +Foxp3 + T cells is decreased in peripheral blood but increased in lesional psoriatic skin of patients with psoriasis. Thus, our study suggests a previously unappreciated role of CD8 +CD25 + Foxp3 + T cells in skin disorders, and induction of these cells in vitro may be an effective immunotherapy for skin inflammation.