Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs

Matthew D. Griffin, Ward H. Lutz, Vy A. Phan, Lori A. Bachman, David J. McKean, Rajiv Kumar

Research output: Contribution to journalArticle

219 Scopus citations

Abstract

We show that the immunosuppressive effects of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) are due, in part, to inhibition of the T cell stimulatory functions of dendritic cells (DCs). Addition of 10-12 and 10-8 M 1α,25(OH)2D3 to murine DC cultures resulted in a concentration-dependent reduction in levels of class II MHC and the co-stimulatory ligands B7-1, B7-2, and CD40 without affecting the number of DCs generated. Higher concentrations of 1α,25(OH)2D3 reduced DC yield. The capacity of DCs to induce proliferation of purified allogeneic T cells was reduced by 1α,25(OH)2D3. The vitamin D3 analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-D3, exerted identical effects at 100-fold lower concentrations. Inhibition of DC maturation and stimulatory function was absent in cultures from mice genetically lacking vitamin D receptors (VDR). Vitamin D analogs effectively reduce DC function via VDR-dependent pathways. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)701-708
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume270
Issue number3
DOIs
StatePublished - Apr 21 2000

Keywords

  • Antigen presentation
  • Autoimmunity
  • CD40
  • CD80
  • CD86
  • Co-stimulation
  • Dendritic cells
  • Immune tolerance
  • Transplantation
  • Vitamin D

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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