Milestones in Photoimmunology

Abstract

Photoimmunology started almost 40 years ago with the discovery of a link between UVR and immunosuppression during experimental photocarcinogenesis. Cutaneous UVR-induced tumors appeared to be highly antigenic, as they were rejected upon inoculation into syngeneic mice (Kripke, 1986). Recipients treated with immunosuppressive drugs did not reject the transplanted tumors, similar to recipients who had received low doses of UVR instead of pharmacological immunosuppression, indicating that UVR suppresses cellular immunity. The most effective UVR spectrum to alter an immune response turned out to be the mid-wave range (UVB, 290–320 nm). Thus, most of the photoimmunologic studies were conducted with UVB, although UVA (320–400 nm) certainly has an effect on immune reactions as well. Besides the development of skin tumors, UVR was found to inhibit contact hypersensitivity (Toews et al., 1980). As mice that received the contact allergen through UVR-exposed skin could not be resensitized against the same antigen a few weeks later, it was concluded that UVR induces long-term suppression. This appeared to be antigen specific, as no other immune responses were altered. As UVR exposure and sensitization affect the same skin area, this model is also referred to as local immunosuppression. Later studies showed that UVR, although at higher doses, can also affect the immune system in a systemic manner via the release of soluble mediators (IL-10, tumor necrosis factor) from the skin (Ullrich and Schmitt, 2000). Whether the alarmin (endogenous mediators released upon cellular injury) IL-33 contributes to UVR-induced immunosuppression awaits further investigation, although the fact that neutralization of IL-33 blocks UVR-induced immunosuppression is quite convincing (Byrne et al., 2011).