Conditional Deletion of TGF-beta R1 Using Langerin-Cre Mice Results in Langerhans Cell Deficiency and Reduced Contact Hypersensitivity

Sonja Zahner, Junda Kel, CAE Martina, Inge Brouwers - Haspels, MA van Roon, Björn Clausen

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59 Citations (Scopus)

Abstract

The critical role of Langerhans cells (LC) in contact hypersensitivity (CHS) was recently questioned in studies using different LC-depletion mouse models. On one hand, inducible ablation of LC led to diminished ear swelling, suggesting functional redundancy between LC and (Langerin(+)) dermal dendritic cells (DC). On the other hand, constitutive or acute depletion of LC resulted in an enhanced reaction, supporting a regulatory role of LC in CHS. To address this controversy by conditional gene targeting, we generated Langerin-Cre knockin mice. Breeding these mice to a Cre-reporter strain demonstrated robust and specific DNA recombination in LC, as well as other Langerin(+) tissue DC. In agreement with the vital requirement of TGF-beta signaling for LC development, crossing Langerin-Cre to mice homozygous for a loxP-flanked TGF-beta R1 allele resulted in permanent LC deficiency, whereas the homeostasis of dermal Langerin(+) DC was unaffected. In the absence of LC, induction of CHS in these Langerin(+) DC-specific TGF-beta R1-deficient mice elicited decreased ear swelling compared with controls. This novel approach provided further evidence against a regulatory function of LC in CHS. Moreover, these Langerin-Cre mice represent a unique and powerful tool to dissect the role and molecular control of Langerin(+) DC populations beyond LC. The Journal of Immunology, 2011, 187: 5069-5076.
Original languageUndefined/Unknown
Pages (from-to)5069-5076
Number of pages8
JournalJournal of Immunology
Volume187
Issue number10
DOIs
Publication statusPublished - 2011

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