Conditional Deletion of TGF-βR1 Using Langerin-Cre Mice Results in Langerhans Cell Deficiency and Reduced Contact Hypersensitivity
| Autor: | Sonja Zahner, Björn E. Clausen, Inge Brouwers-Haspels, Cerithsa A. E. Martina, Marian A. van Roon, Junda M. Kel |
|---|---|
| Přispěvatelé: | Other departments, Immunology |
| Rok vydání: | 2011 |
| Předmět: |
Langerhans cell
Langerin Transgene Immunology Receptor Transforming Growth Factor-beta Type I Mice Transgenic Protein Serine-Threonine Kinases Mice Antigens CD medicine Animals Immunology and Allergy Lectins C-Type Gene Knock-In Techniques Receptor Mice Knockout Regulation of gene expression Integrases integumentary system biology Gene targeting Dendritic Cells Cell biology Disease Models Animal Mannose-Binding Lectins medicine.anatomical_structure Gene Expression Regulation Langerhans Cells Dermatitis Allergic Contact Gene Targeting biology.protein Receptors Transforming Growth Factor beta Gene Deletion Homeostasis Transforming growth factor |
| Zdroj: | Journal of immunology (Baltimore, Md., 187(10), 5069-5076. American Association of Immunologists Journal of Immunology, 187(10), 5069-5076. American Association of Immunologists |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1101880 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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