PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells.
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Szatmari I, Pap A, Ruhl R, Ma JX, Illarionov PA, Besra GS, Rajnavolgyi E, Dezso B, Nagy L
PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells.
J Exp Med. 2006 Oct 2;203(10):2351-62. Epub 2006 Sep 18.
- PubMed ID
- 16982809 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Vitamin A Retinal dehydrogenase 2 Protein Humans UnknownSubstrateDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Rosiglitazone Approved Investigational ADA 100 upregulated rosiglitazone results in increased expression of ADA mRNA 20q13.12 Rosiglitazone Approved Investigational AGPAT4 56895 upregulated rosiglitazone results in increased expression of AGPAT4 mRNA 6q26 Rosiglitazone Approved Investigational AGRN 375790 downregulated rosiglitazone results in decreased expression of AGRN mRNA 1p36.33 Rosiglitazone Approved Investigational AJAP1 55966 upregulated rosiglitazone results in increased expression of AJAP1 mRNA 1p36.32 Rosiglitazone Approved Investigational ALDH1A2 8854 upregulated rosiglitazone results in increased expression of ALDH1A2 mRNA 15q21.3 Rosiglitazone Approved Investigational APLP2 334 upregulated rosiglitazone results in increased expression of APLP2 mRNA 11q24.3 Rosiglitazone Approved Investigational ATP2B1 490 downregulated rosiglitazone results in decreased expression of ATP2B1 mRNA 12q21.33 Rosiglitazone Approved Investigational B3GNT4 79369 upregulated rosiglitazone results in increased expression of B3GNT4 mRNA 12q24.31 Rosiglitazone Approved Investigational BAG2 9532 upregulated rosiglitazone results in increased expression of BAG2 mRNA 6p12.1 Rosiglitazone Approved Investigational CALCRL 10203 downregulated rosiglitazone results in decreased expression of CALCRL mRNA 2q32.1 Rosiglitazone Approved Investigational CARD14 79092 upregulated rosiglitazone results in increased expression of CARD14 mRNA 17q25.3 Rosiglitazone Approved Investigational CD1A 909 downregulated rosiglitazone results in decreased expression of CD1A mRNA 1q23.1 Rosiglitazone Approved Investigational CD1D 912 upregulated rosiglitazone results in increased expression of CD1D mRNA 1q23.1 Rosiglitazone Approved Investigational CD300A 11314 upregulated rosiglitazone results in increased expression of CD300A mRNA 17q25.1 Rosiglitazone Approved Investigational CD300LB 124599 upregulated rosiglitazone results in increased expression of CD300LB mRNA 17q25.1 Rosiglitazone Approved Investigational CD300LF 146722 upregulated rosiglitazone results in increased expression of CD300LF mRNA 17q25.1 Rosiglitazone Approved Investigational CDR2L 30850 downregulated rosiglitazone results in decreased expression of CDR2L mRNA 17q25.1 Rosiglitazone Approved Investigational COL5A3 50509 upregulated rosiglitazone results in increased expression of COL5A3 mRNA 19p13.2 Rosiglitazone Approved Investigational CTTNBP2 83992 downregulated rosiglitazone results in decreased expression of CTTNBP2 mRNA 7q31.31 Rosiglitazone Approved Investigational DCSTAMP 81501 upregulated rosiglitazone results in increased expression of DCSTAMP mRNA 8q22.3 Rosiglitazone Approved Investigational DHRS3 9249 upregulated rosiglitazone results in increased expression of DHRS3 mRNA 1p36.21 Rosiglitazone Approved Investigational DHRS9 10170 upregulated rosiglitazone results in increased expression of DHRS9 mRNA 2q31.1 Rosiglitazone Approved Investigational DMPK 1760 downregulated rosiglitazone results in decreased expression of DMPK mRNA 19q13.32 Rosiglitazone Approved Investigational DMWD 1762 downregulated rosiglitazone results in decreased expression of DMWD mRNA 19q13.32 Rosiglitazone Approved Investigational DNAJC5B 85479 upregulated rosiglitazone results in increased expression of DNAJC5B mRNA 8q13.1 Rosiglitazone Approved Investigational EHF 26298 upregulated rosiglitazone results in increased expression of EHF mRNA 11p13 Rosiglitazone Approved Investigational EML4 27436 upregulated rosiglitazone results in increased expression of EML4 mRNA 2p21 Rosiglitazone Approved Investigational ETS2 2114 upregulated rosiglitazone results in increased expression of ETS2 mRNA 21q22.2 Rosiglitazone Approved Investigational FABP4 2167 upregulated rosiglitazone results in increased expression of FABP4 mRNA 8q21.13 Rosiglitazone Approved Investigational FAM109A 144717 downregulated rosiglitazone results in decreased expression of FAM109A mRNA 12q24.12 Rosiglitazone Approved Investigational FAR2 55711 upregulated rosiglitazone results in increased expression of FAR2 mRNA 12p11.22 Rosiglitazone Approved Investigational FBXO15 201456 upregulated rosiglitazone results in increased expression of FBXO15 mRNA 18q22.3 Rosiglitazone Approved Investigational FN1 2335 upregulated rosiglitazone results in increased expression of FN1 mRNA 2q35 Rosiglitazone Approved Investigational FUT7 2529 downregulated rosiglitazone results in decreased expression of FUT7 mRNA 9q34.3 Rosiglitazone Approved Investigational GABARAPL1 23710 upregulated rosiglitazone results in increased expression of GABARAPL1 mRNA 12p13.2 Rosiglitazone Approved Investigational GDF15 9518 upregulated rosiglitazone results in increased expression of GDF15 mRNA 19p13.11 Rosiglitazone Approved Investigational GOLGA8A 23015 downregulated rosiglitazone results in decreased expression of GOLGA8A mRNA 15q14 Rosiglitazone Approved Investigational GPD1L 23171 downregulated rosiglitazone results in decreased expression of GPD1L mRNA 3p22.3 Rosiglitazone Approved Investigational GUSB 2990 upregulated rosiglitazone results in increased expression of GUSB mRNA 7q11.21 Rosiglitazone Approved Investigational HIPK2 28996 upregulated rosiglitazone results in increased expression of HIPK2 mRNA 7q34 Rosiglitazone Approved Investigational HIST1H2BD 3017 downregulated rosiglitazone results in decreased expression of HIST1H2BD mRNA 6p22.2 Rosiglitazone Approved Investigational HLX 3142 downregulated rosiglitazone results in decreased expression of HLX mRNA 1q41 Rosiglitazone Approved Investigational IL1R1 3554 downregulated rosiglitazone results in decreased expression of IL1R1 mRNA 2q11.2-q12.1 Rosiglitazone Approved Investigational IL1RAP 3556 downregulated rosiglitazone results in decreased expression of IL1RAP mRNA 3q28 Rosiglitazone Approved Investigational INPP5F 22876 upregulated rosiglitazone results in increased expression of INPP5F mRNA 10q26.11 Rosiglitazone Approved Investigational IPCEF1 26034 downregulated rosiglitazone results in decreased expression of IPCEF1 mRNA 6q25.2 Rosiglitazone Approved Investigational ITGAE 3682 upregulated rosiglitazone results in increased expression of ITGAE mRNA 17p13.2 Rosiglitazone Approved Investigational KIAA0040 9674 downregulated rosiglitazone results in decreased expression of KIAA0040 mRNA 1q25.1 Rosiglitazone Approved Investigational KIAA1161 57462 downregulated rosiglitazone results in decreased expression of KIAA1161 mRNA 9p13.3 Rosiglitazone Approved Investigational KIFC2 90990 downregulated rosiglitazone results in decreased expression of KIFC2 mRNA 8q24.3 Rosiglitazone Approved Investigational LAIR1 3903 upregulated rosiglitazone results in increased expression of LAIR1 mRNA 19q13.42 Rosiglitazone Approved Investigational LDLRAD4 753 upregulated rosiglitazone results in increased expression of LDLRAD4 mRNA 18p11.21 Rosiglitazone Approved Investigational LELP1 149018 downregulated rosiglitazone results in decreased expression of LELP1 mRNA 1q21.3 Rosiglitazone Approved Investigational LILRA1 11024 upregulated rosiglitazone results in increased expression of LILRA1 mRNA 19q13.42 Rosiglitazone Approved Investigational LRP11 84918 downregulated rosiglitazone results in decreased expression of LRP11 mRNA 6q25.1 Rosiglitazone Approved Investigational MAN1C1 57134 downregulated rosiglitazone results in decreased expression of MAN1C1 mRNA 1p36.11 Rosiglitazone Approved Investigational MAP3K6 9064 downregulated rosiglitazone results in decreased expression of MAP3K6 mRNA 1p36.11 Rosiglitazone Approved Investigational MAP4K1 11184 downregulated rosiglitazone results in decreased expression of MAP4K1 mRNA 19q13.1-q13.4 Rosiglitazone Approved Investigational METRN 79006 downregulated rosiglitazone results in decreased expression of METRN mRNA 16p13.3 Rosiglitazone Approved Investigational MGAT4C 25834 downregulated rosiglitazone results in decreased expression of MGAT4C mRNA 12q21.31-q21.32 Rosiglitazone Approved Investigational NDRG2 57447 downregulated rosiglitazone results in decreased expression of NDRG2 mRNA 14q11.2 Rosiglitazone Approved Investigational NRIP1 8204 upregulated rosiglitazone results in increased expression of NRIP1 mRNA 21q11.2-q21.1 Rosiglitazone Approved Investigational NUDT7 283927 downregulated rosiglitazone results in decreased expression of NUDT7 mRNA 16q23.1 Rosiglitazone Approved Investigational OLR1 4973 upregulated rosiglitazone results in increased expression of OLR1 mRNA 12p13.2 Rosiglitazone Approved Investigational OMA1 115209 upregulated rosiglitazone results in increased expression of OMA1 mRNA 1p32.2-p32.1 Rosiglitazone Approved Investigational PALD1 27143 downregulated rosiglitazone results in decreased expression of PALD1 mRNA 10q22.1 Rosiglitazone Approved Investigational PAPSS2 9060 upregulated rosiglitazone results in increased expression of PAPSS2 mRNA 10q23.2-q23.31 Rosiglitazone Approved Investigational PDLIM2 64236 downregulated rosiglitazone results in decreased expression of PDLIM2 mRNA 8p21.3 Rosiglitazone Approved Investigational PDLIM4 8572 downregulated rosiglitazone results in decreased expression of PDLIM4 mRNA 5q31.1 Rosiglitazone Approved Investigational PHLDA2 7262 downregulated rosiglitazone results in decreased expression of PHLDA2 mRNA 11p15.4 Rosiglitazone Approved Investigational PLBD1 79887 upregulated rosiglitazone results in increased expression of PLBD1 mRNA 12p13.1 Rosiglitazone Approved Investigational PLPP3 8613 upregulated rosiglitazone results in increased expression of PLPP3 mRNA 1p32.2 Rosiglitazone Approved Investigational PON2 5445 downregulated rosiglitazone results in decreased expression of PON2 mRNA 7q21.3 Rosiglitazone Approved Investigational PRAM1 84106 upregulated rosiglitazone results in increased expression of PRAM1 mRNA 19p13.2 Rosiglitazone Approved Investigational QPRT 23475 downregulated rosiglitazone results in decreased expression of QPRT mRNA 16p11.2 Rosiglitazone Approved Investigational RAB15 376267 downregulated rosiglitazone results in decreased expression of RAB15 mRNA 14q23.3 Rosiglitazone Approved Investigational RAB20 55647 upregulated rosiglitazone results in increased expression of RAB20 mRNA 13q34 Rosiglitazone Approved Investigational RAP1GAP 5909 downregulated rosiglitazone results in decreased expression of RAP1GAP mRNA 1p36.12 Rosiglitazone Approved Investigational RBKS 64080 upregulated rosiglitazone results in increased expression of RBKS mRNA 2p23.2 Rosiglitazone Approved Investigational RBP1 5947 upregulated rosiglitazone results in increased expression of RBP1 mRNA 3q23 Rosiglitazone Approved Investigational RDH10 157506 upregulated rosiglitazone results in increased expression of RDH10 mRNA 8q21.11 Rosiglitazone Approved Investigational REPS2 9185 downregulated rosiglitazone results in decreased expression of REPS2 mRNA Xp22.2 Rosiglitazone Approved Investigational RFLNB 359845 upregulated rosiglitazone results in increased expression of RFLNB mRNA 17p13.3 Rosiglitazone Approved Investigational RFXAP 5994 downregulated rosiglitazone results in decreased expression of RFXAP mRNA 13q13.3 Rosiglitazone Approved Investigational RHOBTB3 22836 upregulated rosiglitazone results in increased expression of RHOBTB3 mRNA 5q15 Rosiglitazone Approved Investigational RPIA 22934 upregulated rosiglitazone results in increased expression of RPIA mRNA 2p11.2 Rosiglitazone Approved Investigational SEL1L3 23231 upregulated rosiglitazone results in increased expression of SEL1L3 mRNA 4p15.2 Rosiglitazone Approved Investigational SELPLG 6404 downregulated rosiglitazone results in decreased expression of SELPLG mRNA 12q24.11 Rosiglitazone Approved Investigational SIGLEC17P 284367 upregulated rosiglitazone results in increased expression of SIGLEC17P mRNA 19q13.41 Rosiglitazone Approved Investigational SIRPB1 10326 upregulated rosiglitazone results in increased expression of SIRPB1 mRNA 20p13 Rosiglitazone Approved Investigational SLC26A11 284129 upregulated rosiglitazone results in increased expression of SLC26A11 mRNA 17q25.3 Rosiglitazone Approved Investigational SLITRK4 139065 upregulated rosiglitazone results in increased expression of SLITRK4 mRNA Xq27.3 Rosiglitazone Approved Investigational SNAI3 333929 upregulated rosiglitazone results in increased expression of SNAI3 mRNA 16q24.3 Rosiglitazone Approved Investigational SSMEM1 136263 downregulated rosiglitazone results in decreased expression of SSMEM1 mRNA 7q32.2 Rosiglitazone Approved Investigational TACSTD2 4070 downregulated rosiglitazone results in decreased expression of TACSTD2 mRNA 1p32.1 Rosiglitazone Approved Investigational TBC1D2 55357 upregulated rosiglitazone results in increased expression of TBC1D2 mRNA 9q22.33 Rosiglitazone Approved Investigational TBL1X 6907 downregulated rosiglitazone results in decreased expression of TBL1X mRNA Xp22.31-p22.2 Rosiglitazone Approved Investigational TBL2 26608 upregulated rosiglitazone results in increased expression of TBL2 mRNA 7q11.23 Rosiglitazone Approved Investigational TGM2 7052 upregulated rosiglitazone results in increased expression of TGM2 mRNA 20q11.23 Rosiglitazone Approved Investigational THBS3 7059 upregulated rosiglitazone results in increased expression of THBS3 mRNA 1q22 Rosiglitazone Approved Investigational TMEM14A 28978 downregulated rosiglitazone results in decreased expression of TMEM14A mRNA 6p12.2 Rosiglitazone Approved Investigational TNFSF12 8742 downregulated rosiglitazone results in decreased expression of TNFSF12 mRNA 17p13.1 Rosiglitazone Approved Investigational TNS1 7145 downregulated rosiglitazone results in decreased expression of TNS1 mRNA 2q35 Rosiglitazone Approved Investigational WFS1 7466 upregulated rosiglitazone results in increased expression of WFS1 mRNA 4p16.1 Rosiglitazone Approved Investigational ZBTB7B 51043 downregulated rosiglitazone results in decreased expression of ZBTB7B mRNA 1q21.3 Tretinoin Approved Investigational Nutraceutical TGM2 7052 upregulated Tretinoin results in increased expression of TGM2 mRNA 20q11.23