Exposure to ultraviolet radiation causes dendritic cells/macrophages to secrete immune-suppressive IL-12p40 homodimers

UV-induced immune suppression is a risk factor for sunlight-induced skin ca ncer. Exposure to UV radiation has been shown to suppress the rejection of highly antigenic UV-induced skin cancers, suppresses delayed and contact hy persensitivity, and depress the ability of dendritic cells to present Ag to T cells. One consequence of UV exposure is altered activation of T cell su bsets, APCs from UV-irradiated mice fail to present Ag to Th1 T cells; howe ver, Ag presentation to Th2 T tells is normal. While this has been known fo r some time, the mechanism behind the preferential suppression of Th1 cell activation has yet to be explained. We tested the hypothesis that this sele ctive impairment of APC function results from altered cytokine production. We found that dendritic cells/macrophages (DC/M phi) from UV-irradiated mic e failed to secrete biologically active IL-12 following in vitro stimulatio n with LPS, Instead, DC/M phi isolated from the lymphoid organs of UV-irrad iated mice secreted IL-12p40 homodimer, a natural antagonist of biologicall y active IL-12, Furthermore, when culture supernatants from UV-derived DC/M phi were added to IL-12-activated T cells, IFN-gamma secretion was totally suppressed, indicating that the IL-12p40 homodimer found in the supernatan t fluid was biologically active. We suggest that by suppressing DC/M phi IL -12p70 secretion while promoting IL-12p40 homodimer secretion, UV exposure preferentially suppress the activation of Th1 cells, thereby suppressing Th -1 cell-driven inflammatory immune reactions.