Ultraviolet-B radiation upregulates expression of dectin-2 on epidermal langerhans cells by activating the gene promoter
Ultraviolet-B radiation upregulates expression of dectin-2 on epidermal langerhans cells by activating the gene promoter
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DOI：
10.1562/2004-10-21-rc-349r.1
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发表时间：
2005-07-01
影响因子：
3.3
通讯作者：
Cruz, PD
中科院分区：
文献类型：
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作者：
Bonkobara, M;Yagihara, H;Cruz, PD
表皮朗格汉斯细胞(LC)属于树突状细胞抗原提呈细胞(APC)家族，能启动抗原特异性免疫反应或耐受反应。在小鼠中，我们已经展示了紫外线-B(UV-B)照射通过将LC从免疫原性转化为耐受性APC来诱导对接触性超敏反应的长期抑制(耐受)。C型凝集素受体Dectin-2由LC和树突状细胞优先表达，也被证明参与诱导这种形式的UV-B诱导的免疫抑制。这些观察结果使我们质疑UV-B是否可以通过LC调节Dectin-2的表达。在设计表达Dectin-2基因启动子并连接到荧光素酶报告基因的ICR小鼠中，我们发现体内宽带UVB处理可以激活LC中的启动子。在野生型C3H/HEN小鼠中，我们发现这样的处理在体内产生了LC，并在mRNA和蛋白水平上增加了Dectin-2的表达。这些小鼠的骨髓来源的树突状细胞经宽带UV-B体外处理后，也显示Dectin-2mRNA的表达上调。这些发现使我们得出结论，宽带UV-B通过激活Dectin-2基因启动子上调LC中Dectin-2的表达。这种扩增表明，UV-B诱导的免疫抑制可能(至少部分)是由于LC中Dectin-2表达的增强。
Epidermal Langerhans cells (LC) belong to the antigen-presenting cell (APC) family of dendritic cells that can initiate antigen-specific immunogenic or tolerogenic responses. In mice, we have shown ultraviolet-B (UV-B) irradiation to induce long-lasting suppression (tolerance) of contact hypersensitivity responses by converting LC from immunogenic to tolerogenic APC. The C-type lectin receptor, dectin-2, expressed preferentially by LC and dendritic cells, has also been shown to be involved in inducing this form of UV-B-induced immunosuppression. These observations led us to question whether UV-B can modulate dectin-2 expression by LC. In ICR mice engineered to express the dectin-2 gene promoter linked to a luciferase reporter gene, we found broadband UVB treatment in vivo to activate the promoter in LC. In wildtype C3H/HeN mice, we found such treatment in vivo to yield LC with increased dectin-2 expression at both mRNA and protein levels. Broadband UV-B treatment in vitro of bone marrow-derived dendritic cells from these mice also showed upregulated expression of dectin-2 mRNA. These findings lead us to conclude that broadband UV-B upregulates dectin-2 expression in LC by activating the dectin-2 gene promoter. Such amplification suggests that UV-B-induced immunosuppression may be due (at least in part) to augmented dectin-2 expression in LC.