DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27.
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.
Sigmundsdottir
Hekla
H
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Pan
Junliang
J
Debes
Gudrun F
GF
Alt
Carsten
C
Habtezion
Aida
A
Soler
Dulce
D
Butcher
Eugene C
EC
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism*; D002762:Cholecalciferol / Q000378:metabolism*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D054447:Receptors, CCR10; D018167:Receptors, Calcitriol / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013472:Sunlight; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
C492276:CCL27 protein, human; C515706:CCR10 protein, human; D054425:Chemokine CCL27; D019742:Chemokines, CC; D054447:Receptors, CCR10; D018167:Receptors, Calcitriol; D019707:Receptors, Chemokine; D018664:Interleukin-12; D002762:Cholecalciferol