Abstract
During adaptive immune responses, dendritic cells activate T cells and endow them with specific homing properties. Mechanisms that 'imprint' specific tropisms, however, are not well defined. We show here that 1,25(OH)(2)D(3), the active form of vitamin D3, signaled T cells to express CC chemokine receptor 10, which enabled them to migrate to the skin-specific chemokine CCL27 secreted by keratinocytes of the epidermis. In contrast, 1,25(OH)(2)D(3) suppressed the gut-homing receptors alpha4beta7 and CCR9. Vitamin D3, the inactive prohormone naturally generated in the skin by exposure to the sun, was processed by dendritic cells and T cells to the active metabolite, providing a mechanism for the local regulation of T cell 'epidermotropism'. Our findings support a model in which dendritic cells process and 'interpret' locally produced metabolites to 'program' T cell homing and microenvironmental positioning.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
- Animals
- Antigen Presentation / immunology
- Base Sequence
- Cell Movement / immunology
- Cells, Cultured
- Chemokine CCL27
- Chemokines, CC / immunology
- Chemokines, CC / metabolism*
- Cholecalciferol / metabolism*
- Coculture Techniques
- Dendritic Cells / immunology
- Dendritic Cells / metabolism*
- Flow Cytometry
- Humans
- Interleukin-12 / immunology
- Interleukin-12 / metabolism
- Keratinocytes / immunology
- Keratinocytes / metabolism*
- Lymphocyte Activation / immunology
- Molecular Sequence Data
- Receptors, CCR10
- Receptors, Calcitriol / immunology
- Receptors, Calcitriol / metabolism
- Receptors, Chemokine / biosynthesis*
- Receptors, Chemokine / genetics
- Reverse Transcriptase Polymerase Chain Reaction
- Sheep
- Sunlight
- T-Lymphocytes / immunology
- T-Lymphocytes / metabolism*
Substances
- CCL27 protein, human
- CCR10 protein, human
- Chemokine CCL27
- Chemokines, CC
- Receptors, CCR10
- Receptors, Calcitriol
- Receptors, Chemokine
- Interleukin-12
- Cholecalciferol