Our laboratory is involved in evaluating the effect of environmental influences such as chemical carcinogens and ultraviolet radiation on the skin immune system. The focus of our research is on the role of innate immunity in the development of skin carcinogenesis. Toll-like receptors (TLRs), one component of innate immunity, are intricately associated with a number of dermatologic conditions. We have found that the innate immune system mediates through Toll like receptor-4 (TLR4) signaling to activate the cell mediated adaptive immune response against chemically induced tumors. We are currently in the process of evaluating the role of the innate immune system in ultraviolet B (UVB) radiation induced skin cancer. The mechanisms by which UVB radiation influences cell mediated immune responses have been the subject of extensive investigation. However, there is little information on the role of innate immunity in this process. Our recent experiments suggest that TLR4, may play an important role in photoimmunosuppression. Currently, we are investigating whether the resistance of TLR4 gene knockout mice to UVB-induced DNA damage and immunosuppression has implications for photocarcinogenesis. We are also in the process of evaluating the molecular mechanisms involved in these processes. The ultimate goal of these studies will be to define the role of innate immune receptors in tumor development that occurs following UVB radiation. This may allow us to identify genetic loci that are involved in these processes and to develop immunopreventive and immunotherapeutic approaches toward them.