Acute ablation of Langerhans cells enhances skin immune responses

Aleh Bobr, Irlanda Olvera-Gomez, Botond Z. Igyarto, Krystal M. Haley, Kristin A. Hogquist, Daniel H. Kaplan

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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-diptheria 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.

Original languageEnglish (US)
Pages (from-to)4724-4728
Number of pages5
JournalJournal of Immunology
Volume185
Issue number8
DOIs
StatePublished - Oct 15 2010

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