title: Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions.
abstract: A new langerin(+) DC subset has recently been identified in murine dermis (langerin(+) dDC), but the lineage and functional relationships between these cells and langerin(+) epidermal Langerhans cells (LC) are incompletely characterized. Selective expression of the cell adhesion molecule EpCAM by LC allowed viable LC to be easily distinguished from langerin(+) dDC in skin and lymphoid tissue and ex vivo as well. Differential expression of EpCAM and langerin revealed the presence of at least 3 distinct skin DC subsets. We determined that LC and langerin(+) dDC exhibit different migratory capabilities in vitro and repopulate distinct anatomic compartments in skin at different rates after conditional depletion in vivo. Langerin(+) dDC, in contrast to LC, did not require TGFbeta1 for development. Carefully timed gene gun immunization studies designed to take advantage of the distinct repopulation kinetics of langerin(+) dDC and LC revealed that langerin(+) dDC were required for optimal production of beta-galactosidase-specific IgG2a/c and IgG2b in the acute phase. In contrast, immunization via LC-deficient skin resulted in persistent and strikingly reduced IgG1 and enhanced IgG2a Ab production. Our data support the concepts that LC and langerin(+) dDC represent distinct DC subsets that have specialized functions and that LC are important immunoregulatory cells. The presence of at least 3 functionally distinct skin DC subsets may have particular relevance for vaccines that are administered epicutaneously.
authors.affiliation: Dermatology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagao
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Wolfgang W
authors.initials: WW
authors.lastname: Leitner
authors.forename: Sei-ichiro
authors.initials: S
authors.lastname: Motegi
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Mark C
authors.initials: MC
authors.lastname: Udey
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D005260:Female; D007700:Kinetics; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D053773:Transforming Growth Factor beta1