DCs Metabolize Sunlight-Induced Vitamin D3 to 'Program' T Cell Attraction to the Epidermal Chemokine CCL27

Nat Immunol. 2007 Mar;8(3):285-93. doi: 10.1038/ni1433. Epub 2007 Jan 28.

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

Associated data

  • GEO/GSE6743