Mechanisms by which UV radiation, a natural component of sunlight, suppresses the immune response

The ultraviolet (UV) radiation present in sunlight is the primary cause of skin cancer, the most common form of cancer in the industrialized world. UV exposure is also immunosuppressive, and the immunosuppression induced by sunlight exposure is a major risk factor for skin cancer induction. For this reason, studying the mechanisms underlying UV-mediated immunosuppression has been an active area of research since the initial description of UV-induced immunosuppression and its role in photocarcinogenesis by Margaret Kripke in the early 1970s. Moreover, understanding how this ubiquitous and inescapable environmental agent affects the immune response provides an excellent model system for understanding how the environment influences the immune system. In this chapter I will review some of the more recent findings in this area. I will describe the mechanisms that activate systemic immunosuppression, following a photon of UV light as it penetrates the outermost layers of the skin, and activate photoreceptors, which then starts a cascade of events that ultimately transmits the suppressive signal from the skin to the immune system. I will also briefly describe some of the beneficial effects of UV-induced immunosuppression (i.e., suppressing autoimmunity). Finally, I will review studies demonstrating that applying jet fuel to the skin activates a similar mechanism to induce immunosuppression, indicating that the lessons learned from studying UV-induced immunosuppression may have broader implications for the general toxicology community.