Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions

Keisuke Nagao, Florent Ginhoux, Wolfgang W. Leitner, Sei Ichiro Motegi, Clare L. Bennett, Bj̈orn E. Clausen, Miriam Merad, Mark C. Udey

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

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 TGFβ1 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 β-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.

Original languageEnglish
Pages (from-to)3312-3317
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number9
DOIs
StatePublished - Mar 3 2009

Keywords

  • EpCAM
  • Gene gun
  • Langerin
  • TGF-beta

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