title: Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function.
abstract: Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin(-/-) mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin(-/-) mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin(-/-) LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin(-/-) mice were not impaired in their capacity to process native OVA protein for I-A(b)-restricted presentation to CD4(+) T lymphocytes or for H-2K(b)-restricted cross-presentation to CD8(+) T lymphocytes. langerin(-/-) mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin(-/-) and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin(-/-) C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranee, Parc Scientifique de Luminy, Marseille, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Smina
authors.initials: S
authors.lastname: Aït-Yahia
authors.forename: Valérie
authors.initials: V
authors.lastname: Clair-Moninot
authors.forename: Hella
authors.initials: H
authors.lastname: Stössel
authors.forename: Edgar
authors.initials: E
authors.lastname: Badell
authors.forename: Yann
authors.initials: Y
authors.lastname: Bordat
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Pooley
authors.forename: Thierry
authors.initials: T
authors.lastname: Lang
authors.forename: Eric
authors.initials: E
authors.lastname: Prina
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coste
authors.forename: Olivia
authors.initials: O
authors.lastname: Gresser
authors.forename: Toufic
authors.initials: T
authors.lastname: Renno
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Romani
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Sem
authors.initials: S
authors.lastname: Saeland
authors.forename: Patrice
authors.initials: P
authors.lastname: Douillard
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000941:Antigens / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology*; D001755:Blastocyst / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002273:Carcinogens; D002465:Cell Movement; D002468:Cell Physiological Phenomena; D003594:Cytoplasmic Granules / Q000378:metabolism; D003713:Dendritic Cells; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D004622:Embryo, Mammalian / Q000166:cytology; D005434:Flow Cytometry; D005822:Genetic Vectors; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology; D007700:Kinetics; D007801:Langerhans Cells / Q000166:cytology*; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics* / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced; D010047:Ovalbumin / Q000378:metabolism; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology
chemical_list: D000941:Antigens; D000954:Antigens, Surface; D002273:Carcinogens; C498497:Cd207 protein, mouse; D037102:Lectins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D015127:9,10-Dimethyl-1,2-benzanthracene; D010047:Ovalbumin