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.

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
doi.org/10.1073/pnas.0807126106, hdl.handle.net/1765/18052
Proceedings of the National Academy of Sciences of the United States of America
Erasmus MC: University Medical Center Rotterdam

Nagao, K., Ginhoux, F., Leitner, W., Motegi, S. I., Bennett, C., Clausen, B., … Udey, M. (2009). Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions. Proceedings of the National Academy of Sciences of the United States of America, 106(9), 3312–3317. doi:10.1073/pnas.0807126106