Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity.
Langerhans cells (LC) form a unique subset of dendritic cells (DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC (dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/DT-based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance.
Bennett
Clare L
CL
Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
van Rijn
Erwin
E
Jung
Steffen
S
Inaba
Kayo
K
Steinman
Ralph M
RM
Kapsenberg
Martien L
ML
Clausen
Björn E
BE
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000503:physiopathology; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D066257:Heparin-binding EGF-like Growth Factor; D007108:Immune Tolerance / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology*
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D004167:Diphtheria Toxin; 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; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins