The relationship between DNA damage and immunosuppression by ultraviolet radiation

皮肤是一个重要的免疫器官，由多种免疫活性细胞组成。由于皮肤是最外层的器官，因此皮肤的免疫学功能受到紫外线辐射的损害。首先，我们研究了中波紫外线（UVR）对接触性超敏反应的诱导作用。多种因素，包括UVR总剂量、UVR分次照射、半抗原浓度和应用区域，可调节局部和全身UVR诱导的免疫抑制。紫外线辐射的致癌作用已经众所周知。基于dna损伤的基因突变被认为是紫外线辐射致癌的主要作用。因此，有DNA损伤修复缺陷的着色性干皮病（XP）患者很容易发生皮肤癌。然而，最近已经阐明，uvr诱导的肿瘤免疫抑制也参与其中。我们发现，通过基因靶向建立的XP模型小鼠不仅容易发生皮肤癌，而且在紫外线照射下容易发生急性炎症和免疫抑制。提示dna损伤、紫外线炎症与免疫抑制之间可能存在密切关系。此外，UVR还能显著抑制自然杀伤细胞的活性。最近我们发现，在U-yR照射下，XP小鼠皮肤可以产生大量的前列腺素。我们现在正在研究过量的前列腺素是否可以解释炎症增强、免疫抑制和NK细胞活性受损。

The skin is an important immune organ which is composed of various immune competent cells. linmunologic functions of the skin are impaired by ultraviolet radiation(UVR), since the skin is an outermost organ.First, we investigated the effect of mid-wave uv(UVR) on the induction of contact hypersensitivity. A variety of factors including total dose of UVR, devided UVR exposure, hapten concentration, and application area, modulated local and systemic UVR-induced inmiunosuppression.The carcinogenesis of UVR has been well known. Gene-mutations based on the DNA-damage had been belived to be a main action of UVR in the carcinogenesis. Therefore, skin cancers easily develop in patients with xeroderma pigmentosum(XP) who have a defect in repair of DNA damage. Recently, however, it has been elucidated that UVR-induced suppression of tumor immunity is also involved. We demonstrated that XP modelambda mice, which were established by gene-targetting, easily develop not only skin cancers but also acute inflanunation and immunosuppression by UVR.This suggests that there may be close relationships among DNA-damage, UV-inflammation and immunosuppression. Furtheremore, UVR greatly suppressed the activity of natural killer cells. Most recently we found that XP mouse skin can produce a great amount of prostaglandins after irradiation of U-yR.We are now investigating if excess amounts of prostaglandins can explain the enhanced inflammation, immunosuppression and impaired NK cell activity.