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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3271-3280. Prepublished online as a Blood First Edition Paper on July 30, 2007; DOI 10.1182/blood-2007-06-096222. This Article Full Text (PDF) Supplemental Figure and Tables All Versions of this Article: blood-2007-06-096222v1 110/9/3271    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Szatmari, I. Articles by Nagy, L. Search for Related Content PubMed PubMed Citation Articles by Szatmari, I. Articles by Nagy, L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 15, 2007 Accepted July 25, 2007 PPAR regulates the function of human dendritic cells primarily by altering lipid metabolism Istvan Szatmari, Daniel Torocsik, Maura Agostini, Tibor Nagy, Mark Gurnell, Endre Barta, Krishna Chatterjee, and Laszlo Nagy* Department of Biochemostry & Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary Department of Medicine, University of Cambridge, Cambridge, United Kingdom Department of Bioinformatics, Agricultural Biotechnology Center, Godollo, Hungary * Corresponding author; email: lnagy{at}indi.biochem.dote.hu. Activation of the lipid-regulated nuclear receptor, Peroxisome Proliferator-Activated Receptor gamma (PPAR) modifies the immunophenotype of monocyte-derived dendritic cells (DCs). However it has not been analyzed in a systematic manner how lipid metabolism and immune regulation are connected at the transcriptional level via this receptor. Here we present the genome-wide expression analyses of PPAR-instructed human DCs. Receptor activation was achieved by exogenous, synthetic as well as endogenous, natural means. Over 1000 transcripts are regulated during DC development by activation of PPAR, half of the changes are positive effects. These changes appear to enhance and modulate the robust gene expression alterations associated with monocyte to DC transition. Strikingly, only genes related to lipid metabolism are over-represented among early-induced genes. As a net consequence lipid accumulation appears to be diminished in these cells. In contrast, genes related to immune response are regulated after 24 hours implying the existence of indirect mechanisms of modulation. Receptor-dependence was established by using DCs of patients harboring a dominant negative mutation of PPAR. Our data show that PPAR acts as a mostly positive transcriptional regulator in human developing DCs acting primarily through controlling genes involved in lipid metabolism and via this, indirectly modifying the immune phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Linking metabolism to immunity through PPAR Chaitra Marathe and Peter Tontonoz Blood 2007 110: 3092-3093. [Full Text] [PDF] This article has been cited by other articles: L. Klotz, S. Burgdorf, I. Dani, K. Saijo, J. Flossdorf, S. Hucke, J. Alferink, N. Novak, M. Beyer, G. Mayer, et al. The nuclear receptor PPAR{gamma} selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity J. Exp. Med., September 28, 2009; 206(10): 2079 - 2089. [Abstract] [Full Text] [PDF] P. E. Almeida, A. R. Silva, C. M. Maya-Monteiro, D. Torocsik, H. D'Avila, B. Dezso, K. G. Magalhaes, H. C. Castro-Faria-Neto, L. Nagy, and P. T. Bozza Mycobacterium bovis Bacillus Calmette-Guerin Infection Induces TLR2-Dependent Peroxisome Proliferator-Activated Receptor {gamma} Expression and Activation: Functions in Inflammation, Lipid Metabolism, and Pathogenesis J. Immunol., July 15, 2009; 183(2): 1337 - 1345. [Abstract] [Full Text] [PDF] L. Szeles, G. Keresztes, D. Torocsik, Z. Balajthy, L. Krenacs, S. Poliska, A. Steinmeyer, U. Zuegel, M. Pruenster, A. Rot, et al. 1,25-Dihydroxyvitamin D3 Is an Autonomous Regulator of the Transcriptional Changes Leading to a Tolerogenic Dendritic Cell Phenotype J. Immunol., February 15, 2009; 182(4): 2074 - 2083. [Abstract] [Full Text] [PDF] C. Gelin, I. Sloma, D. Charron, and N. Mooney Regulation of MHC II and CD1 antigen presentation: from ubiquity to security J. Leukoc. Biol., February 1, 2009; 85(2): 215 - 224. [Abstract] [Full Text] [PDF] F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, J. Diaz-Delfin, M. A. de Madariaga, and J. C. Domingo Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR{gamma}:RXR heterodimers: comparison with other polyunsaturated fatty acids J. Leukoc. Biol., October 1, 2008; 84(4): 1172 - 1182. [Abstract] [Full Text] [PDF] N. Dobrosi, B. I. Toth, G. Nagy, A. Dozsa, T. Geczy, L. Nagy, C. C. Zouboulis, R. Paus, L. Kovacs, and T. Biro Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling FASEB J, October 1, 2008; 22(10): 3685 - 3695. [Abstract] [Full Text] [PDF] A. Are, L. Aronsson, S. Wang, G. Greicius, Y. K. Lee, J.-A. Gustafsson, S. Pettersson, and V. Arulampalam Enterococcus faecalis from newborn babies regulate endogenous PPAR{gamma} activity and IL-10 levels in colonic epithelial cells PNAS, February 12, 2008; 105(6): 1943 - 1948. [Abstract] [Full Text] [PDF]

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