title: Langerhans cells arise from monocytes in vivo.
abstract: Langerhans cells (LCs) are the only dendritic cells of the epidermis and constitute the first immunological barrier against pathogens and environmental insults. The factors regulating LC homeostasis remain elusive and the direct circulating LC precursor has not yet been identified in vivo. Here we report an absence of LCs in mice deficient in the receptor for colony-stimulating factor 1 (CSF-1) in steady-state conditions. Using bone marrow chimeric mice, we have established that CSF-1 receptor-deficient hematopoietic precursors failed to reconstitute the LC pool in inflamed skin. Furthermore, monocytes with high expression of the monocyte marker Gr-1 (also called Ly-6c/G) were specifically recruited to the inflamed skin, proliferated locally and differentiated into LCs. These results identify Gr-1(hi) monocytes as the direct precursors for LCs in vivo and establish the importance of the CSF-1 receptor in this process.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
authors.forename: Milena
authors.initials: M
authors.lastname: Bogunovic
authors.forename: Martine
authors.initials: M
authors.lastname: Loubeau
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Dai
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism
chemical_list: C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D016173:Macrophage Colony-Stimulating Factor