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

Biochem Biophys Res Commun. 2000 Apr 21;270(3):701-8. doi: 10.1006/bbrc.2000.2490.

Abstract

We show that the immunosuppressive effects of 1alpha, 25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) are due, in part, to inhibition of the T cell stimulatory functions of dendritic cells (DCs). Addition of 10(-12) and 10(-8) M 1alpha,25(OH)(2)D(3) 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 1alpha,25(OH)(2)D(3) reduced DC yield. The capacity of DCs to induce proliferation of purified allogeneic T cells was reduced by 1alpha,25(OH)(2)D(3). The vitamin D(3) analog, 1alpha,25(OH)(2)-16-ene-23-yne-26,27-hexafluoro-19-nor -D(3), 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcitriol / analogs & derivatives
  • Calcitriol / pharmacology*
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Cholecalciferol / analogs & derivatives*
  • Cholecalciferol / pharmacology
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / immunology
  • Histocompatibility Antigens Class II / analysis
  • Integrin alphaXbeta2 / analysis
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Calcitriol / deficiency
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / physiology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • 1,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-D3
  • Histocompatibility Antigens Class II
  • Integrin alphaXbeta2
  • Receptors, Calcitriol
  • Cholecalciferol
  • Calcitriol