Behavioral responses of epidermal Langerhans cells in situ to local pathological stimuli
Behavioral responses of epidermal Langerhans cells in situ to local pathological stimuli
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DOI：
10.1038/sj.jid.5700107
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发表时间：
2006-04-01
影响因子：
6.5
通讯作者：
Takashima, Akira
中科院分区：
文献类型：
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作者：
Nishibu, Akiko;Ward, Brant R.;Takashima, Akira
病理刺激引起树突状细胞（DC）的基因表达、表面表型和功能的协调变化，从而促进适应性免疫应答的诱导。DC成熟的概念主要是通过研究表皮朗格汉斯细胞（LC）来建立的，表皮朗格汉斯细胞是环境界面上的一种原型未成熟DC亚群。利用I-A β增强的绿色荧光蛋白（EGFP）基因敲入小鼠，可以在完整皮肤中观察到LCs，我们通过延时共聚焦显微镜记录了EGFP（+）LCs的动态运动。LC表现出一种独特的行为，称为树突监视伸展和收缩循环习惯（dSEARCH），其特征是树突通过角质形成细胞之间的细胞间隙有节奏地伸展和收缩。在皮肤器官培养或皮下注射肿瘤坏死因子α后进行监测时，LC显示角质形成细胞之间的扩增的dendritis和阿米巴样侧向迁移。活体成像实验进一步揭示了5-10%的LC中的稳态dSEARCH运动。局部应用反应性半抗原DNFB可增强LC的粘附并触发LC的侧向迁移。这些观察结果引入了一个新的概念，即LC的原位成熟进一步伴随着运动活动的协调重编程。
Pathological stimuli provoke coordinated changes in gene expression, surface phenotype, and function of dendritic cells (DCs), thereby facilitating the induction of adaptive immune responses. This concept of DC maturation was established mainly by studying epidermal Langerhans cells (LCs), a prototypic immature DC subset at the environmental interface. Taking advantage of I-A beta-enhanced green fluorescent protein (EGFP) knock-in mice in which LCs can be visualized in intact skin, we recorded the dynamic movement of EGFP(+) LCs by time-lapse confocal microscopy. LCs exhibited a unique behavior, termed dendrite surveillance extension and retraction cycling habitude (dSEARCH), characterized by rhythmic extension and retraction of dendrites through intercellular spaces between keratinocytes. When monitored after skin organ culture or subcutaneous injection of tumor necrosis factor alpha, LCs showed amplified dSEARCH and amoeba-like lateral migration between keratinocytes. Intravital imaging experiments further revealed steady-state dSEARCH motion in 5-10% of LCs. Topical application of a reactive hapten, DNFB, augmented dSEARCH and triggered lateral migration of LC in vivo. These observations introduce a new concept that in situ maturation of LCs is further accompanied by coordinated reprogramming of motile activities.