1. ¹Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
2. ²Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
3. ³Department of Pathology, Harvard Medical School, Boston, Massachussetts, USA

Correspondence: Professor Akira Takashima, Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, USA. E-mail: akira.takashima@utsouthwestern.edu

⁴These authors contributed equally to this work

Received 23 September 2005; Revised 31 October 2005; Accepted 31 October 2005; Published online 26 January 2006.

Abstract

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-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 , 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.