title: Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity.
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.
authors: Department of Immunology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
authors: Sonja P
authors: SP
authors: Zahner
authors: Junda M
authors: JM
authors: Kel
authors: Cerithsa A E
authors: CA
authors: Martina
authors: Inge
authors: I
authors: Brouwers-Haspels
authors: Marian A
authors: MA
authors: van Roon
authors: Björn E
authors: BE
authors: Clausen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D055879:Gene Knock-In Techniques / Q000379:methods; D018390:Gene Targeting; D019426:Integrases / Q000235:genetics*; D007801:Langerhans Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C045073:Cre recombinase; D019426:Integrases