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Blood, 15 January 2007, Vol. 109, No. 2, pp. 643-652. Prepublished online as a Blood First Edition Paper on September 12, 2006; DOI 10.1182/blood-2006-04-016840. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-016840v1 109/2/643    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 Gogolak, P. Articles by Rajnavolgyi, E. Search for Related Content PubMed PubMed Citation Articles by Gogolak, P. Articles by Rajnavolgyi, E. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Differentiation of CD1a– and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPAR Peter Gogolak1, Bence Rethi1,4, Istvan Szatmari2, Arpad Lanyi1, Balazs Dezso3, Laszlo Nagy2, and Eva Rajnavolgyi1, 1 Institute of Immunology, 2 Institute of Biochemistry and Molecular Biology, and 3 Department of Pathology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary; 4 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation and CD1 expression, but the mechanisms by which exogenous factors confer these effects are poorly understood. Here we describe the dependence of CD1a– monocyte-derived dendritic cell (moDC) development on lipids associated with the expression of peroxisome proliferator-activated receptor–gamma (PPAR). We also show the consecutive differentiation of immature CD1a–PPAR+ moDCs to CD1a+PPAR– cells limited by serum lipoproteins and terminated by proinflammatory cytokines. Immature CD1a– moDCs possess higher internalizing capacity than CD1a+ cells, whereas both activated subtypes have similar migratory potential but differ in their cytokine and chemokine profiles, which translates to distinct T-lymphocyte–polarizing capacities. CD1a+ moDCs stand out by their capability to secrete high amounts of IL-12p70 and CCL1. As lipoproteins skew moDC differentiation toward the generation of CD1a–PPAR+ cells and inhibit the development of CD1a+PPAR– cells, we suggest that the uptake of lipids results in endogenous PPAR agonists that induce a cascade of gene transcription coordinating lipid metabolism, the expression of lipid-presenting CD1 molecules, subtype dichotomy, and function. The presence of CD1a–PPAR+ and CD1a+PPAR– DCs in lymph nodes and in pulmonary Langerhans cell histiocytosis confirms the functional relevance of these DC subsets in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Zsiros, K. Kis-Toth, P. Hajdu, R. Gaspar, J. Bielanska, A. Felipe, E. Rajnavolgyi, and G. Panyi Developmental Switch of the Expression of Ion Channels in Human Dendritic Cells J. Immunol., October 1, 2009; 183(7): 4483 - 4492. [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] S. Mariotti, V. Sargentini, C. Marcantonio, E. Todero, R. Teloni, M. C. Gagliardi, A. R. Ciccaglione, and R. Nisini T-cell-mediated and antigen-dependent differentiation of human monocyte into different dendritic cell subsets: a feedback control of Th1/Th2 responses FASEB J, September 1, 2008; 22(9): 3370 - 3379. [Abstract] [Full Text] [PDF] A. Smed-Sorensen, M. Moll, T.-Y. Cheng, K. Lore, A.-C. Norlin, L. Perbeck, D. B. Moody, A.-L. Spetz, and J. K. Sandberg IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via Fc{gamma}RIIa Blood, May 15, 2008; 111(10): 5037 - 5046. [Abstract] [Full Text] [PDF] I. Szatmari, D. Torocsik, M. Agostini, T. Nagy, M. Gurnell, E. Barta, K. Chatterjee, and L. Nagy PPAR{gamma} regulates the function of human dendritic cells primarily by altering lipid metabolism Blood, November 1, 2007; 110(9): 3271 - 3280. [Abstract] [Full Text] [PDF]

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