PMID- 16982809
OWN - NLM
STAT- MEDLINE
DCOM- 20061213
LR  - 20220129
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 203
IP  - 10
DP  - 2006 Oct 2
TI  - PPARgamma controls CD1d expression by turning on retinoic acid synthesis in 
      developing human dendritic cells.
PG  - 2351-62
AB  - Dendritic cells (DCs) expressing CD1d, a molecule responsible for lipid antigen 
      presentation, are capable of enhancing natural killer T (iNKT) cell 
      proliferation. The signals controlling CD1 expression and lipid antigen 
      presentation are poorly defined. We have shown previously that stimulation of the 
      lipid-activated transcription factor, peroxisome proliferator-activated receptor 
      (PPAR)gamma, indirectly regulates CD1d expression. Here we demonstrate that 
      PPARgamma, turns on retinoic acid synthesis by inducing the expression of retinol 
      and retinal metabolizing enzymes such as retinol dehydrogenase 10 and 
      retinaldehyde dehydrogenase type 2 (RALDH2). PPARgamma-regulated expression of 
      these enzymes leads to an increase in the intracellular generation of all-trans 
      retinoic acid (ATRA) from retinol. ATRA regulates gene expression via the 
      activation of the retinoic acid receptor (RAR)alpha in human DCs, and RARalpha 
      acutely regulates CD1d expression. The retinoic acid-induced elevated expression 
      of CD1d is coupled to enhanced iNKT cell activation. Furthermore, in vivo 
      relevant lipids such as oxidized low-density lipoprotein can also elicit retinoid 
      signaling leading to CD1d up-regulation. These data show that regulation of 
      retinoid metabolism and signaling is part of the PPARgamma-controlled 
      transcriptional events in DCs. The uncovered mechanisms allow the DCs to respond 
      to altered lipid homeostasis by changing CD1 gene expression.
FAU - Szatmari, Istvan
AU  - Szatmari I
AD  - Department of Biochemistry and Molecular Biology, University of Debrecen, Medical 
      and Health Science Center, Debrecen H-4010, Hungary.
FAU - Pap, Attila
AU  - Pap A
FAU - Ruhl, Ralph
AU  - Ruhl R
FAU - Ma, Jiang-Xing
AU  - Ma JX
FAU - Illarionov, Petr A
AU  - Illarionov PA
FAU - Besra, Gurdyal S
AU  - Besra GS
FAU - Rajnavolgyi, Eva
AU  - Rajnavolgyi E
FAU - Dezso, Balazs
AU  - Dezso B
FAU - Nagy, Laszlo
AU  - Nagy L
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - G0400421/MRC_/Medical Research Council/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060918
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antigens, CD1)
RN  - 0 (Antigens, CD1d)
RN  - 0 (CD1D protein, human)
RN  - 0 (PPAR gamma)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.105 (retinol dehydrogenase)
SB  - IM
MH  - Alcohol Oxidoreductases/metabolism
MH  - Antigens, CD1/*metabolism
MH  - Antigens, CD1d
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Dendritic Cells/*metabolism
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Enzymologic/*immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - Microarray Analysis
MH  - PPAR gamma/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*immunology
MH  - Tretinoin/*metabolism
PMC - PMC2118109
EDAT- 2006/09/20 09:00
MHDA- 2006/12/14 09:00
PMCR- 2007/04/02
CRDT- 2006/09/20 09:00
PHST- 2006/09/20 09:00 [pubmed]
PHST- 2006/12/14 09:00 [medline]
PHST- 2006/09/20 09:00 [entrez]
PHST- 2007/04/02 00:00 [pmc-release]
AID - jem.20060141 [pii]
AID - 20060141 [pii]
AID - 10.1084/jem.20060141 [doi]
PST - ppublish
SO  - J Exp Med. 2006 Oct 2;203(10):2351-62. doi: 10.1084/jem.20060141. Epub 2006 Sep 
      18.