Prevention of UV radiation-induced immunosuppression by IL-12 is dependent on DNA repair.
The immunostimulatory cytokine IL-12 is able to antagonize immunosuppression induced by solar/ultraviolet (UV) radiation via yet unknown mechanisms. IL-12 was recently found to induce deoxyribonucleic acid (DNA) repair. UV-induced DNA damage is an important molecular trigger for UV-mediated immunosuppression. Thus, we initiated studies into immune restoration by IL-12 to discern whether its effects are linked to DNA repair. IL-12 prevented both UV-induced suppression of the induction of contact hypersensitivity and the depletion of Langerhans cells, the primary APC of the skin, in wild-type but not in DNA repair-deficient mice. IL-12 did not prevent the development of UV-induced regulatory T cells in DNA repair-deficient mice. In contrast, IL-12 was able to break established UV-induced tolerance and inhibited the activity of regulatory T cells independent of DNA repair. These data identify a new mechanism by which IL-12 can restore immune responses and also demonstrate a link between DNA repair and the prevention of UV-induced immunosuppression by IL-12.
Schwarz
Agatha
A
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, D-48149 Münster, Germany.
Maeda
Akira
A
Kernebeck
Kerstin
K
van Steeg
Harry
H
Beissert
Stefan
S
Schwarz
Thomas
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007107:Immune System / Q000187:drug effects* / Q000528:radiation effects*; D007165:Immunosuppression Therapy; D018664:Interleukin-12 / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D018664:Interleukin-12