Acute ablation of Langerhans cells enhances skin immune responses

J Immunol. 2010 Oct 15;185(8):4724-8. doi: 10.4049/jimmunol.1001802. Epub 2010 Sep 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Cell Separation
  • Dermatitis, Contact / immunology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Knock-In Techniques
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Langerhans Cells / immunology*
  • Lectins, C-Type / genetics
  • Mannose-Binding Lectins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Skin / cytology
  • Skin / immunology*


  • Antigens, CD
  • CD207 protein, human
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Mannose-Binding Lectins