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Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function
Adrien Kissenpfennig1, Smina Aït-Yahia, Valérie Clair-Moninot
1Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranee, Parc Scientifique de Luminy, Marseille, France.
Insights
Mice lacking langerin, a receptor on Langerhans cells (LC), show no developmental or functional deficits. This langerin-deficient mouse model is valuable for studying LC functions and Birbeck granule roles.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Langerin is a C-type lectin found on Langerhans cells (LC), a subset of dendritic leukocytes.
- Langerin functions as a cell surface receptor, inducing the formation of Birbeck granules (BG), an LC-specific organelle.
Purpose of the Study:
- To investigate the role of langerin and Birbeck granules in LC function.
- To characterize the phenotype and function of langerin-deficient mice.
Main Methods:
- Generation of a langerin knockout mouse model (langerin-/-) on a C57BL/6 background.
- Phenotypic analysis of LC, including BG presence and cell surface markers.
- Functional assays assessing antigen capture, migration, maturation, antigen presentation (CD4+ and CD8+ T cells), pathogen susceptibility, and skin tumor development.
Main Results:
- langerin-/- mice exhibited normal macroscopic development and LC numbers in the epidermis, but lacked BG.
- LC from langerin-/- mice showed no other phenotypic alterations and retained normal functions in antigen capture, migration, and maturation.
- Antigen presentation to CD4+ and CD8+ T cells, susceptibility to microorganisms, and skin tumor development rates were comparable between langerin-/- and wild-type mice.
Conclusions:
- Langerin and Birbeck granules are dispensable for several key LC functions, including antigen presentation and immune responses.
- The generated langerin-/- C57BL/6 mouse is a valuable tool for future research into langerin's specific roles and the functional significance of BG.
Abstract:
Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin(-/-) mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin(-/-) mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin(-/-) LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin(-/-) mice were not impaired in their capacity to process native OVA protein for I-A(b)-restricted presentation to CD4(+) T lymphocytes or for H-2K(b)-restricted cross-presentation to CD8(+) T lymphocytes. langerin(-/-) mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin(-/-) and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin(-/-) C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG.
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