Article abstract


Nature Immunology 8, 285 - 293 (2007)
Published online: 28 January 2007 | doi:10.1038/ni1433

DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27

Hekla Sigmundsdottir1,2,4, Junliang Pan1,2,4, Gudrun F Debes1,2, Carsten Alt1,2, Aida Habtezion1,2, Dulce Soler3 & Eugene C Butcher1,2


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)2D3, 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)2D3 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.

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  1. Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
  2. The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
  3. Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
  4. These authors contributed equally to this work.

Correspondence to: Eugene C Butcher1,2 e-mail: ebutcher@stanford.edu

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