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A postmigrational switch among skin-derived dendritic cells to a macrophage-like phenotype is predetermined by the intracutaneous cytokine balance.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Jun 15; Vol. 176 (12), pp. 7232-42. - Publication Year :
- 2006
-
Abstract
- Migration of dendritic cells (DC) to secondary lymphoid organs under proinflammatory conditions coincides with their maturation and acquisition of T cell stimulatory abilities. In contrast, impaired activation of DC, e.g., in tumor-conditioned environments, may hamper their activation and possibly their subsequent migration to lymph nodes, leading to either immunological tolerance or ignorance, respectively. In this study, the influence of cytokines in the peripheral skin microenvironment on the activation state of migrating cutaneous DC was assessed using an ex vivo human skin explant model. We observed a phenotypic shift from mature CD83(+) DC to immature CD14(+) macrophage-like cells within 7 days subsequent to migration from unconditioned skin. These macrophage-like cells displayed a poor T cell stimulatory ability and lacked expression of CCR7, thus precluding their migration to paracortical T cell areas in the lymph nodes. The balance of suppressive and stimulatory cytokines during the initiation of migration decided the postmigrational fate of DC with IL-10 accelerating and GM-CSF and IL-4 preventing the phenotypic switch, which proved irreversible once established. These observations indicate that, in immunosuppressed environments, a postmigrational DC-to-macrophage shift may hinder T cell activation, but also that it may be prevented by prior conditioning of the tissue microenvironment by GM-CSF and/or IL-4.
- Subjects :
- Biomarkers metabolism
Cell Differentiation immunology
Cell Proliferation
Cytokines physiology
Dendritic Cells cytology
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Granulocyte-Macrophage Colony-Stimulating Factor physiology
Humans
Immunophenotyping
Interleukin-4 pharmacology
Interleukin-4 physiology
Langerhans Cells immunology
Langerhans Cells metabolism
Lipopolysaccharide Receptors biosynthesis
Macrophages cytology
Organ Culture Techniques
Skin metabolism
Stem Cells immunology
Stem Cells metabolism
Cell Movement immunology
Cytokines biosynthesis
Dendritic Cells immunology
Dendritic Cells metabolism
Macrophages immunology
Macrophages metabolism
Skin cytology
Skin immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 176
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 16751366
- Full Text :
- https://doi.org/10.4049/jimmunol.176.12.7232