Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions.
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.
Nagao
Keisuke
K
Dermatology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
Ginhoux
Florent
F
Leitner
Wolfgang W
WW
Motegi
Sei-ichiro
S
Bennett
Clare L
CL
Clausen
Björn E
BE
Merad
Miriam
M
Udey
Mark C
MC
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
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D053773:Transforming Growth Factor beta1