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

Acute ablation of Langerhans cells enhances skin immune responses.

Author information

1
Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.

Abstract

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.

PMID:
20855870
PMCID:
PMC3050031
DOI:
10.4049/jimmunol.1001802
[Indexed for MEDLINE]
Free PMC Article

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