Nishibu Akiko, Ward Brant R, Boes Marianne, Takashima Akira
Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
J Dermatol Sci. 2007 Jan;45(1):23-30. doi: 10.1016/j.jdermsci.2006.10.003. Epub 2006 Nov 22.
To understand the behavioral biology of Langerhans cells (LCs), we recently recorded time-lapse images of LCs in the knock-in mice expressing the I-Abeta chain tagged with the enhanced green fluorescence protein (EGFP). EGFP(+) LCs showed relatively limited motility in the steady state, whereas topical application of dinitrofluorobenzene (DNFB) markedly augmented a unique movement of dendrites characterized by rhythmic extension and retraction, termed dSEARCH, and triggered amoeba-like lateral migration of cell bodies.
To define underlying mechanisms by which hapten treatment alters LC behaviors.
The I-Abeta-EGFP mice received subcutaneous (s.c.) injection of recombinant IL-1alpha or TNFalpha (50 ng/animal) and dynamic behaviors of EGFP(+) LCs were recorded by time-lapse confocal microscopy at several time points to measure their dSEARCH activities and lateral migration. In a different set of experiments, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor-2 (sTNFR2) (0.5 microg/animal) was s.c. injected into the ear skin 30 min before topical application of DNFB, and LC behaviors analyzed 30 h later.
Local injection of IL-1alpha or TNFalpha induced significant, albeit modest, augmentation of both dSEARCH and lateral migration. Co-injection of TNFalpha and IL-1alpha further exacerbated motile activities in a synergistic manner by similar magnitudes observed after DNFB application. Conversely, DNFB-induced behavioral changes were inhibited completely by local injection of IL-1Ra or sTNFR2.
IL-1 and TNFalpha serve as equally important mediators of hapten-induced alteration of LC behaviors. Motile activities of epidermal LCs are reprogrammed by selected cytokines known to be produced by keratinocytes under pathological conditions.
为了解朗格汉斯细胞（LCs）的行为生物学特性，我们最近在表达增强型绿色荧光蛋白（EGFP）标记的I-Aβ链的基因敲入小鼠中记录了LCs的延时图像。在稳态下，EGFP（+）LCs的运动相对受限，而局部应用二硝基氟苯（DNFB）显著增强了一种独特的树突运动，其特征为有节奏的伸展和收缩，称为dSEARCH，并触发细胞体的阿米巴样侧向迁移。
确定半抗原处理改变LC行为的潜在机制。
给I-Aβ-EGFP小鼠皮下注射重组IL-1α或TNFα（50 ng/只动物），并在几个时间点通过延时共聚焦显微镜记录EGFP（+）LCs的动态行为，以测量其dSEARCH活性和侧向迁移。在另一组实验中，在局部应用DNFB前30分钟，将IL-1受体拮抗剂（IL-1Ra）或可溶性TNF受体-2（sTNFR2）（0.5 μg/只动物）皮下注射到耳部皮肤，30小时后分析LC行为。
局部注射IL-1α或TNFα诱导dSEARCH和侧向迁移均有显著增强，尽管增幅较小。TNFα和IL-1α共同注射以协同方式进一步加剧了运动活性，其幅度与应用DNFB后观察到的相似。相反，局部注射IL-1Ra或sTNFR2可完全抑制DNFB诱导的行为变化。
IL-1和TNFα是半抗原诱导LC行为改变的同等重要的介质。表皮LCs的运动活性由病理条件下已知由角质形成细胞产生的特定细胞因子重新编程。
