title: Behavioral responses of epidermal Langerhans cells in situ to local pathological stimuli.
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-Abeta-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.
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishibu
authors.forename: Brant R
authors.initials: BR
authors.lastname: Ward
authors.forename: James V
authors.initials: JV
authors.lastname: Jester
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.forename: Akira
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins