Acute ablation of Langerhans cells enhances skin immune responses.
Understanding the function of Langerhans cells (LCs) in vivo has been complicated by conflicting results from LC-deficient mice. Human Langerin-DTA mice constitutively lack LCs and develop exaggerated contact hypersensitivity (CHS) responses. Murine Langerin-diphtheria toxin receptor (DTR) mice allow for the inducible elimination of LCs and Langerin(+) dermal dendritic cells (dDCs) after administration of diphtheria toxin, which results in reduced CHS. When Langerin(+) dDCs have partially repopulated the skin but LCs are still absent, CHS returns to normal. Thus, LCs appear to be suppressive in human Langerin-DTA mice and redundant in murine Langerin-DTR mice. To determine whether inducible versus constitutive LC ablation explains these results, we engineered human Langerin-DTR mice in which diphtheria toxin ablates LCs without affecting Langerin(+) dDCs. The inducible ablation of LCs in human Langerin-DTR mice resulted in increased CHS. Thus, LC-mediated suppression does not require their absence during ontogeny or during the steady-state and is consistent with a model in which LCs actively suppress Ag-specific CHS responses.
Bobr
Aleh
A
Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Olvera-Gomez
Irlanda
I
Igyarto
Botond Z
BZ
Haley
Krystal M
KM
Hogquist
Kristin A
KA
Kaplan
Daniel H
DH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002469:Cell Separation; D003877:Dermatitis, Contact / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055879:Gene Knock-In Techniques; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics; D037241:Mannose-Binding Lectins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012867:Skin / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; C121916:CD207 protein, human; C587883:HBEGF protein, human; 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