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Cited by 599

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Dendritic cell modulation by 1α,25 dihydroxyvitamin D3and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo

Open access
Griffin, Matthew D., Lutz, Ward, Phan, Vy A., Bachman, Lori A., McKean, David J., Kumar, Rajiv·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.121172198
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Abstract

Dendritic cells (DCs) play a central role in regulating immune activation and responses to self. DC maturation is central to the outcome of antigen presentation to T cells. Maturation of DCs is inhibited by physiological levels of 1α,25 dihydroxyvitamin D 3[1α,25(OH)2 D 3] and a related analog, 1α,25(OH)2-16-ene-23-yne-26,27-hexafluoro-19-nor-vitamin D 3(D 3 analog). Conditioning of bone marrow cultures with 10−10 M D 3 analog resulted in accumulation of immature DCs with reduced IL-12 secretion and without induction of transforming growth factor β1. These DCs retained an immature phenotype after withdrawal of D 3 analog and exhibited blunted responses to maturing stimuli (CD40 ligation, macrophage products, or lipopolysaccharide). Resistance to maturation depended on the presence of the 1α,25(OH)2 D 3 receptor (VDR). In an in vivo model of DC-mediated antigen-specific sensitization, D 3 analog-conditioned DCs failed to sensitize and, instead, promoted prolonged survival of subsequent skin grafts expressing the same antigen. To investigate the physiologic significance of 1α,25(OH)2 D 3/VDR-mediated modulation of DC maturity we analyzed DC populations from mice lacking VDR. Compared with wild-type animals, VDR-deficient mice had hypertrophy of subcutaneous lymph nodes and an increase in mature DCs in lymph nodes but not spleen. We conclude that 1α,25(OH)2 D 3/VDR mediates physiologically relevant inhibition of DC maturity that is resistant to maturational stimuli and modulates antigen-specific immune responses in vivo.

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Cited by

Metadata

Authors
Griffin, M. D., Lutz, W., Phan, V. A., Bachman, L. A., McKean, D. J., & Kumar, R.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2001-05-22
Volume
98
Issue
12
Pages
6800-6805
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.121172198
OpenAlex
W2007751085
Cited by
599
References
1
FWCI
8.83
Type
journal article
Language
en
Open access
green

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