Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs.
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.
Griffin
M D
MD
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. griffin.matthew@mayo.edu
Lutz
W H
WH
Phan
V A
VA
Bachman
L A
LA
McKean
D J
DJ
Kumar
R
R
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016167:Integrin alphaXbeta2 / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
C408047:1,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-D3; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D002117:Calcitriol