A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression.
A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression.
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DOI：
10.4049/jimmunol.160.8.3783
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发表时间：
1998-04
影响因子：
4.4
通讯作者：
V. Shreedhar;T. Giese;Victor W. Sung;S. Ullrich
中科院分区：
文献类型：
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作者：
V. Shreedhar;T. Giese;Victor W. Sung;S. Ullrich
尽管太阳辐射的紫外线波长所含的所有能量都被表皮和真皮上层吸收，但紫外线照射可以抑制远处未照射部位对银的免疫反应。此外，来自许多实验室的数据表明，紫外线照射的一个后果是抑制Th1细胞的激活，而正常或增强Th2细胞的激活，导致Th2样表型的转变。紫外线照射的角质形成细胞分泌的细胞因子，特别是IL-10，已被证明在诱导全身免疫抑制和T辅助细胞亚群的差异激活中起主要作用。尽管IL-10可以通过改变Ag的呈递和抑制ifn - γ的分泌来影响Th1细胞的活化，但Th2应答的主要信号是IL-4。在这里，我们验证了紫外线照射诱导IL-4分泌的假设。紫外线照射诱导血清IL-4呈剂量依赖性。紫外线照射小鼠注射抗il -4阻断免疫抑制。然而，我们没有发现任何证据支持紫外线照射的角质形成细胞分泌IL-4。相反，我们认为照射的角化细胞释放的前列腺素诱导血清IL-4，因为用环氧化酶-2抑制剂治疗紫外线照射的小鼠可阻断其产生。此外，我们发现用抗il -4治疗紫外线照射小鼠可抑制血清IL-10水平。此外，正常小鼠注射PGE2诱导血清IL-4和IL-10。我们认为紫外线照射激活了细胞因子级联反应（PGE2—> IL-4—> IL-10），最终导致全身免疫抑制。
Even though all of the energy contained with the UV wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress immune responses to Ag introduced at distant nonirradiated sites. In addition, data from a number of laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinoctyes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets. Although IL-10 can influence Th1 cell activation by altering Ag presentation and suppressing IFN-gamma secretion, the major signal for the development of a Th2 response is IL-4. Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV-irradiated mice with anti-IL-4 blocked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prostaglandins released by irradiated keratinocytes induce serum IL-4 since treating UV-irradiated mice with a cyclooxygenase-2 inhibitor blocked its production. Moreover, we found that treating UV-irradiated mice with anti-IL-4 suppressed serum IL-10 levels. In addition, injecting normal mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV exposure activates a cytokine cascade (PGE2 --> IL-4 --> IL-10) that ultimately results in systemic immune suppression.