Conditional Deletion of TGF-βR1 Using Langerin-Cre Mice Results in Langerhans Cell Deficiency and Reduced Contact Hypersensitivity

  • Zahner S
  • Kel J
  • Martina C
 et al. 
  • 23

    Readers

    Mendeley users who have this article in their library.
  • 40

    Citations

    Citations of this article.

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-β signaling for LC development, crossing Langerin-Cre to mice homozygous for a loxP-flanked TGF-βR1 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-βR1-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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Sonja P. Zahner

  • Junda M. Kel

  • Cerithsa A. E. Martina

  • Inge Brouwers-Haspels

  • Marian A. van Roon

  • Björn E. Clausen

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free