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Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin
- Source :
- Scopus-Elsevier
-
Abstract
- Dendritic cells migrate from the skin to the draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T areas, and thus generate immunity. Migrating dendritic cells encounter physical obstacles, such as basement membranes and collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans cell migration. In this study, we use mouse and human skin explant culture models to further study the role of MMPs in the migration and maturation of skin dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of dendritic cells from the skin, but not from other sources. They are also expressed in migrating Langerhans cells in situ. The migration of both Langerhans cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2 define a functional role for MMP-2 in addition to the previously described function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient mice in which Langerhans cell migration from skin explants was strikingly reduced. However, MMP-9 was only required for Langerhans cell migration and not maturation, since nonmigrating Langerhans cells isolated from the epidermis matured normally with regard to morphology, phenotype, and T cell stimulatory function. These data underscore the importance of MMPs, and they may be of relevance for therapeutically regulating dendritic cell migration in clinical vaccination approaches.
- Subjects :
- Pathology
medicine.medical_specialty
Langerhans cell
Matrix metalloproteinase inhibitor
Cellular differentiation
T cell
Immunology
Human skin
Biology
Matrix Metalloproteinase Inhibitors
Basement Membrane
Mice
Organ Culture Techniques
Cell Movement
medicine
Immunology and Allergy
Animals
Humans
Protease Inhibitors
Dendritic cell migration
Histiocyte
Cells, Cultured
Skin
Mice, Knockout
Mice, Inbred BALB C
Follicular dendritic cells
Dose-Response Relationship, Drug
Cell Differentiation
Dendritic Cells
Dermis
Matrix Metalloproteinases
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Epidermal Cells
Matrix Metalloproteinase 9
Langerhans Cells
Matrix Metalloproteinase 2
Epidermis
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....76046cfe3cbc8d730a73ef21a82605d3