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

doi:10.1006/bbrc.2000.2490

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

Nephrology and Hypertension

Research output: Contribution to journal › Article › peer-review

226 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 language	English (US)
Pages (from-to)	701-708
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	270
Issue number	3
DOIs	https://doi.org/10.1006/bbrc.2000.2490
State	Published - 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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10.1006/bbrc.2000.2490

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title = "Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs",

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.",

keywords = "Antigen presentation, Autoimmunity, CD40, CD80, CD86, Co-stimulation, Dendritic cells, Immune tolerance, Transplantation, Vitamin D",

author = "Griffin, {Matthew D.} and Lutz, {Ward H.} and Phan, {Vy A.} and Bachman, {Lori A.} and McKean, {David J.} and Rajiv Kumar",

note = "Funding Information: This work was supported by the Solomon Papper, M.D. Young Investigator Grant of the National Kidney Foundation and by a Mayo Foundation CR20 Award (M.D.G.) as well as by NIH Grants DK-25409 and AR-27032 (R.K.). The authors acknowledge the contributions of James Londowski for expert technical assistance and the staff of the Mayo Foundation Flow Cytometry Core Facility.",

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doi = "10.1006/bbrc.2000.2490",

language = "English (US)",

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AU - Griffin, Matthew D.

AU - Lutz, Ward H.

AU - Phan, Vy A.

AU - Bachman, Lori A.

AU - McKean, David J.

AU - Kumar, Rajiv

N1 - Funding Information: This work was supported by the Solomon Papper, M.D. Young Investigator Grant of the National Kidney Foundation and by a Mayo Foundation CR20 Award (M.D.G.) as well as by NIH Grants DK-25409 and AR-27032 (R.K.). The authors acknowledge the contributions of James Londowski for expert technical assistance and the staff of the Mayo Foundation Flow Cytometry Core Facility.

PY - 2000/4/21

Y1 - 2000/4/21

N2 - 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.

AB - 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.

KW - Antigen presentation

KW - Autoimmunity

KW - CD40

KW - CD80

KW - CD86

KW - Co-stimulation

KW - Dendritic cells

KW - Immune tolerance

KW - Transplantation

KW - Vitamin D

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JO - Biochemical and Biophysical Research Communications

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ER -

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

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