PMID- 11371626
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 12
DP  - 2001 Jun 5
TI  - Dendritic cell modulation by 1alpha,25 dihydroxyvitamin D3 and its analogs: a 
      vitamin D receptor-dependent pathway that promotes a persistent state of 
      immaturity in vitro and in vivo.
PG  - 6800-5
AB  - 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 1alpha,25 dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and a related analog, 
      1alpha,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 beta1. 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 1alpha,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 
      1alpha,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 1alpha,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.
FAU - Griffin, M D
AU  - Griffin MD
AD  - Department of Internal Medicine, Division of Nephrology, Mayo Clinic and 
      Foundation, Rochester, MN 55905, USA. griffin.matthew@mayo.edu
FAU - Lutz, W
AU  - Lutz W
FAU - Phan, V A
AU  - Phan VA
FAU - Bachman, L A
AU  - Bachman LA
FAU - McKean, D J
AU  - McKean DJ
FAU - Kumar, R
AU  - Kumar R
LA  - eng
GR  - R56 AR027032/AR/NIAMS NIH HHS/United States
GR  - AR-27032/AR/NIAMS NIH HHS/United States
GR  - DK-25409/DK/NIDDK NIH HHS/United States
GR  - R01 DK058546/DK/NIDDK NIH HHS/United States
GR  - R01 DK025409/DK/NIDDK NIH HHS/United States
GR  - R01 AR027032/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010522
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Transforming Growth Factor beta)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Antigens, CD/analysis
MH  - B7-1 Antigen/analysis
MH  - B7-2 Antigen
MH  - Calcitriol/analogs & derivatives/*pharmacology
MH  - Dendritic Cells/*drug effects/physiology
MH  - Female
MH  - Male
MH  - Membrane Glycoproteins/analysis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Calcitriol/*physiology
MH  - Skin Transplantation
MH  - Transforming Growth Factor beta/biosynthesis
PMC - PMC34433
EDAT- 2001/05/24 10:00
MHDA- 2001/06/29 10:01
PMCR- 2001/12/05
CRDT- 2001/05/24 10:00
PHST- 2001/05/24 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/05/24 10:00 [entrez]
PHST- 2001/12/05 00:00 [pmc-release]
AID - 121172198 [pii]
AID - 1721 [pii]
AID - 10.1073/pnas.121172198 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6800-5. doi: 10.1073/pnas.121172198. 
      Epub 2001 May 22.