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 cancer. Exposure to UV radiation has been shown to suppress the rejection of highly antigenic UV-induced skin cancers, suppresses delayed and contact hypersensitivity, and depress the ability of dendritic cells to present Ag to T cells. One consequence of UV exposure is altered activation of T cell subsets. APCs from UV-irradiated mice fail to present Ag to Th1 T cells; however, Ag presentation to Th2 T cells is normal. While this has been known for some time, the mechanism behind the preferential suppression of Th1 cell activation has yet to be explained. We tested the hypothesis that this selective impairment of APC function results from altered cytokine production. We found that dendritic cells/macrophages (DC/Mphi) from UV-irradiated mice failed to secrete biologically active IL-12 following in vitro stimulation with LPS. Instead, DC/Mphi isolated from the lymphoid organs of UV-irradiated mice secreted IL-12p40 homodimer, a natural antagonist of biologically active IL-12. Furthermore, when culture supernatants from UV-derived DC/Mphi were added to IL-12-activated T cells, IFN-gamma secretion was totally suppressed, indicating that the IL-12p40 homodimer found in the supernatant fluid was biologically active. We suggest that by suppressing DC/Mphi 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.
Schmitt
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DA
Department of Immunology, University of Texas, M. D. Anderson Cancer Center, and Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Ullrich
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SE
D000818:Animals; D002474:Cell-Free System; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects*; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018189:Immunomagnetic Separation; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology / Q000528:radiation effects*; D018664:Interleukin-12 / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D014466:Ultraviolet Rays
D007166:Immunosuppressive Agents; D018664:Interleukin-12