title: The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells.
abstract: 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.
authors: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Case 906, 13288 Marseille Cedex 9, France.
authors: Lionel Franz
authors: LF
authors: Poulin
authors: Sandrine
authors: S
authors: Henri
authors: Béatrice
authors: B
authors: de Bovis
authors: Elisabeth
authors: E
authors: Devilard
authors: Adrien
authors: A
authors: Kissenpfennig
authors: Bernard
authors: B
authors: Malissen
mesh_terms: 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
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D017493:Leukocyte Common Antigens