Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity.
The relative roles of Langerhans cells (LC), dermal dendritic cells (DC), and, in particular, the recently discovered Langerin(+) dermal DC subset in the induction and control of contact hypersensitivity (CHS) responses remain controversial. Using an inducible mouse model, in which LC and other Langerin(+) DC can be depleted by injection of diphtheria toxin, we previously reported impaired transport of topically applied antigen to draining lymph nodes and reduced CHS in the absence of all Langerin(+) skin DC. In this study, we demonstrate that mice with a selective depletion of LC exhibit attenuated CHS only upon sensitization with a low hapten dose but not with a high hapten dose. In contrast, when painting a higher concentration of hapten onto the skin, which leads to increased antigen dissemination into the dermis, CHS is still diminished in mice lacking all Langerin(+) skin DC. Taken together, these data suggest that the magnitude of a CHS reaction depends on the number of skin DC, which have access to the hapten, rather than on the presence or absence of a particular skin DC population. LC and (Langerin(+)) dermal DC thus seem to have a redundant function in regulating CHS.
Noordegraaf
Madelon
M
Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Flacher
Vincent
V
Stoitzner
Patrizia
P
Clausen
Björn E
BE
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology*; D020405:Dermis / Q000276:immunology / Q000473:pathology; D004167:Diphtheria Toxin / Q000633:toxicity; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D055879:Gene Knock-In Techniques; D006241:Haptens / Q000276:immunology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology*; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009924:Organ Culture Techniques; D011042:Poisons / Q000633:toxicity
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D004167:Diphtheria Toxin; D006241:Haptens; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011042:Poisons