Intravital Imaging of IL-1β Production in Skin
Intravital Imaging of IL-1β Production in Skin
复制标题
DOI：
10.1038/jid.2010.11
复制
发表时间：
2010-06-01
影响因子：
6.5
通讯作者：
Takashima, Akira
中科院分区：
文献类型：
--
作者：
Matsushima, Hironori;Ogawa, Yasushi;Takashima, Akira
IL-1是一种原型炎性细胞因子，在各种皮肤病中具有致病作用。虽然朗格汉斯细胞（LC）已被报道表达IL-1 β mRNA的应用接触敏化剂，它仍然不清楚是否其他类型的细胞产生IL-1 β在皮肤中。因此，我们试图通过构建在IL-1 β启动子控制下表达DsRed荧光蛋白基因的转基因小鼠来直接鉴定活体动物中的IL-1 β产生细胞。在稳态条件下，在皮肤中检测到很少的DsRed荧光信号。在局部应用接触致敏剂恶唑酮后观察到DsRed信号的显著增加，其也诱导显著升高的IL-1 β mRNA和蛋白质表达。DsRed信号主要由表皮和真皮区室中的CD 45（+）/CD 11b（+）髓样白细胞表达，并且仅在小部分表皮LC中检测到。有趣的是，DsRed（+）细胞优先出现在毛囊周围的簇中。活体共聚焦成像实验揭示了DsRed（+）细胞的高运动潜能-它们通过阿米巴样运动不断地在毛囊周围爬行，平均速度为1.0 +/- 0.4 μ m min（-1）（表皮）或2.7 +/- 1.4 μ m min（-1）（真皮）。新开发的体内成像系统代表了用于研究皮肤中IL-1 β产生的空间调节的有用工具。
IL-1 is a prototypic inflammatory cytokine that has pathogenic roles in various skin disorders. Although Langerhans cells (LCs) have been reported to express IL-1 beta mRNA upon application of contact sensitizers, it remains unclear whether other cell types produce IL-1 beta in skin. Thus, we sought to directly identify IL-1 beta-producing cells in living animals by construction of transgenic mice expressing DsRed fluorescence protein gene under the control of IL-1 beta promoter. Little DsRed fluorescence signal was detected in skin under steady-state conditions. Striking increases in DsRed signal were observed after topical application of a contact sensitizer, oxazolone, which also induced markedly elevated IL-1 beta mRNA and protein expression. DsRed signal was expressed primarily by CD45(+)/CD11b(+) myeloid leukocytes in both epidermal and dermal compartments and was detected only in small fractions of epidermal LCs. Interestingly, DsRed(+) cells emerged preferentially as clusters around hair follicles. Intravital confocal imaging experiments revealed highly motile potentials of DsRed(+) cells-they constantly crawled around hair follicles via amoeba-like movements with a mean velocity of 1.0 +/- 0.4 mu m min(-1) (epidermis) or 2.7 +/- 1.4 mu m min(-1) (dermis). The newly developed in vivo imaging system represents a useful tool for studying spatial regulation of IL-1 beta production in skin.