The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells.
Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express the lectin langerin and that reside in their immature state in epidermis. Paradoxically, in mice permitting diphtheria toxin (DT)-mediated ablation of LCs, epidermal LCs reappeared with kinetics that lagged behind that of their putative progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed that a major fraction of the langerin(+), skin-derived DCs found in LNs originates from a developmental pathway that is independent from that of epidermal LCs. This pathway, the existence of which was unexpected, originates in the dermis and gives rise to langerin(+) dermal DCs (DDCs) that should not be confused with epidermal LCs en route to LNs. It explains that after DT treatment, some langerin(+), skin-derived DCs reappear in LNs long before LC-derived DCs. Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin(+) DDCs were found to coexist in wild-type mice. Moreover, DT-mediated ablation of epidermal LCs opened otherwise filled niches and permitted repopulation of adult noninflammatory epidermis with BM-derived LCs. Our results stress that the langerin(+) DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models.
Poulin
Lionel Franz
LF
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Case 906, 13288 Marseille Cedex 9, France.
Henri
Sandrine
S
de Bovis
Béatrice
B
Devilard
Elisabeth
E
Kissenpfennig
Adrien
A
Malissen
Bernard
B
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D020405:Dermis / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D004817:Epidermis / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D007801:Langerhans Cells / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D037241:Mannose-Binding Lectins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D013154:Spleen / Q000378:metabolism
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D017493:Leukocyte Common Antigens