The overall goal of this proposal is to determine in humans the wavelengths responsible for UV induced immunosuppression, potential genetic control mechanisms and whether the immunosuppression can be prevented by pretanning or sunscreens.
In addition to its direct effects on cellular DNA, UV has profound and complex effects on the immune systems which at least in mice induces the generation of T-lymphocytes that suppress immune responses in a long lasting and antigen specific manner (tolerance). The exact mechanisms leading to UV-induced immunosuppression are unknown, but may involve altered function of Langerhans cells, appearance of epidermal macrophages and induction of cytokines which mediate suppression.
In humans UV-radiation has been shown to induce immunosuppression, but the exact wavelength responsible is unknown and may include both UV-B and UV-A. In mice it has been shown that the susceptibility to the deleterious effects of UV-radiation is a genetically determined trait and similar genetic mechanisms in humans may determine those at great risk of developing skin cancer as a consequence of UV-irradiation.
This project is designed to provide answers to the following specific questions :
1. Which wavelength is responsible for UV-induced immunosuppression ?
2. Does this wavelength correlate with wavelengths which are responsible for the altered function and type of epidermal antigen presenting cells and cytokine release ?
3. Is the susceptibility to UV-induced immunosuppression in humans like in mice a genetically determined trait ?
4. Is it possible to prevent the UV-induced immunosuppression with pretanning or sunscreens ?
Funding SchemeCSC - Cost-sharing contracts
SE1 9RT London