Prevention of UV radiation–induced immunosuppression by IL-12 is dependent on DNA repair

Author:

Schwarz Agatha1,Maeda Akira1,Kernebeck Kerstin1,van Steeg Harry2,Beissert Stefan1,Schwarz Thomas13

Affiliation:

1. Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, D-48149 Münster, Germany

2. National Institute of Public Health and the Environment, Laboratory of Health Effects Research, 3720 Bilthoven, Netherlands

3. Department of Dermatology, University Kiel, D-24105 Kiel, Germany

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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