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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 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 Citation Map 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 Immunobiology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY PPAR regulates the function of human dendritic cells primarily by altering lipid metabolism Istvan Szatmari1, Daniel Töröcsik1, Maura Agostini2, Tibor Nagy3, Mark Gurnell2, Endre Barta3, Krishna Chatterjee2, and Laszlo Nagy1 1 Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary; 2 Department of Medicine, University of Cambridge, Cambridge, United Kingdom; and 3 Agricultural Biotechnology Center, Gödöll, Hungary 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. More than 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 overrepresented 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. 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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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