Effect of ultraviolet radiation on Ia expression by keratinocytes

Many skin diseases, such as graft-versus-host disease (GVHD), are marked by lymphocyte infiltrates in the skin. Severity of these diseases is often correlated with the induced expression of class II antigens (human, HLA-DR,; murine, Ia) by the keratinocytes. This suggests that HLA-DR-expressing keratinocytes may be involved in the pathogenesis of these diseases. Since some of these diseases are effectively treated with ultraviolet radiation (UVR), this study was conducted to determine whether UVR alters the keratinocyte expression of class II antigens. To test this hypothesis, 2 models of experimentally induced keratinocyte Ia expression were employed. First, athymic nude mice with one ear protected by electrical tape were exposed to UVR (450 J/m2/day on 4 consecutive days). They were then given an i.v. injection of normal mouse serum (NMS) to induce keratinocyte Ia expression. Keratinocytes in the UVR-exposed skin of these animals were not induced to express Ia; however, Ia-expressing keratinocytes were observed in the epidermis of shielded skin sites. Likewise, it was determined that UVR was capable of downregulating keratinocyte expression of Ia when administered to nude mice 7 d after receiving an injection of NMS. Second, employing a clinically relevant model, we found that Ia expression by keratinocytes in mice undergoing experimentally induced GVHD was abrogated by UVR treatment. This appeared to be a direct effect of the UVR, since keratinocytes in shielded skin sites and mucosal cells in the intestinal epithelium of animals with GVHD were shown to express Ia. These data provide compelling evidence for our hypothesis that decreased HLA-DR expression by keratinocytes in diseased skin treated with UVR is a mechanism by which UVR exerts its therapeutic effect.