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Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2007
- Publisher :
- Rockefeller University Press, 2007.
-
Abstract
- Langerhans cells (LCs) are bone marrow (BM)-derived epidermal dendritic cells (DCs) that develop from precursors found in the dermis. Epidermal LCs are absent in transforming growth factor (TGF) beta1-deficient mice. It is not clear whether TGFbeta1 acts directly on LC precursors to promote maturation or whether it acts on accessory cells, which in turn affect LC precursors. In addition, the physiologic source of TGFbeta1 is uncertain because BM chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGFbeta1 is required for LC development. To address these issues, we created mice transgenic for a bacterial artificial chromosome (BAC) containing the gene for human Langerin into which Cre recombinase had been inserted by homologous recombination (Langerin-Cre). These mice express Cre selectively in LCs, and they were bred to floxed TGFbetaRII and TGFbeta1 mice, thereby generating mice with LCs that either cannot respond to or generate TGFbeta1, respectively. Langerin-Cre TGFbetaRII mice had substantially reduced numbers of epidermal LCs, demonstrating that TGFbeta1 acts directly on LCs in vivo. Interestingly, Langerin-Cre TGFbeta1 mice also had very few LCs both in the steady state and after BM transplantation. Thus, TGFbeta1 derived from LCs acts directly on LCs through an autocrine/paracrine loop, and it is required for LC development and/or survival.
- Subjects :
- Langerhans cell
Langerin
Immunology
Cre recombinase
chemical and pharmacologic phenomena
Mice, Transgenic
Transforming Growth Factor beta1
Mice
03 medical and health sciences
Paracrine signalling
Chimera (genetics)
0302 clinical medicine
Antigens, CD
Genes, Reporter
Skin Physiological Phenomena
medicine
Animals
Humans
Immunology and Allergy
Lectins, C-Type
Autocrine signalling
030304 developmental biology
Recombination, Genetic
0303 health sciences
Integrases
integumentary system
biology
Brief Definitive Report
hemic and immune systems
Cell Biology
Molecular biology
Cell biology
Transplantation
Haematopoiesis
Mannose-Binding Lectins
medicine.anatomical_structure
Langerhans Cells
biology.protein
Brief Definitive Reports
Epidermis
030215 immunology
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 204
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....99ded737969b41f93b3570699589e08d
- Full Text :
- https://doi.org/10.1084/jem.20071401