Schwarz Agatha, Maeda Akira, Kernebeck Kerstin, van Steeg Harry, Beissert Stefan, Schwarz Thomas
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, D-48149 Münster, Germany.
J Exp Med. 2005 Jan 17;201(2):173-9. doi: 10.1084/jem.20041212.
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.
免疫刺激细胞因子白细胞介素-12(IL-12)能够通过尚不清楚的机制拮抗太阳/紫外线(UV)辐射诱导的免疫抑制。最近发现IL-12可诱导脱氧核糖核酸(DNA)修复。紫外线诱导的DNA损伤是紫外线介导的免疫抑制的重要分子触发因素。因此,我们开展了关于IL-12免疫恢复的研究,以确定其作用是否与DNA修复有关。在野生型小鼠而非DNA修复缺陷型小鼠中,IL-12可预防紫外线诱导的接触性超敏反应诱导抑制以及皮肤主要抗原呈递细胞(APC)朗格汉斯细胞的耗竭。IL-12不能预防DNA修复缺陷型小鼠中紫外线诱导的调节性T细胞的产生。相反,IL-12能够打破已建立的紫外线诱导的耐受性,并独立于DNA修复抑制调节性T细胞的活性。这些数据确定了IL-12恢复免疫反应的新机制,也证明了DNA修复与IL-12预防紫外线诱导的免疫抑制之间的联系。