| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
Department of Hematology, Oncology, and Immunology, University of Tübingen, Tübingen, Germany
Dendritic cells (DC) are the most potent APCs known that play a key
role for the initiation of immune responses. Ag presentation to T
lymphocytes is likely a constitutive function of DC that continues
during the steady state. This raises the question of which mechanism(s)
determines whether the final outcome of Ag presentation will be
induction of immunity or of tolerance. In this regard, the mechanisms
controlling DC immunogenicity still remain largely uncharacterized. In
this paper we report that the nuclear receptor peroxisome
proliferator-activated receptor 
(PPAR-), which has
anti-inflammatory properties, redirects DC toward a less
stimulatory mode. We show that activation of PPAR- during DC
differentiation profoundly affects the expression of costimulatory
molecules and of the DC hallmarker CD1a. PPAR- activation in DC
resulted in a reduced capacity to activate lymphocyte proliferation and
to prime Ag-specific CTL responses. This effect might depend on the
decreased expression of costimulatory molecules and on the impaired
cytokine secretion, but not on increased IL-10 production, because this
was reduced by PPAR- activators. Moreover, activation of PPAR- in
DC inhibited the expression of EBI1 ligand chemokine and CCR7, both
playing a pivotal role for DC migration to the lymph nodes. These
effects were accompanied by down-regulation of LPS-induced nuclear
localized RelB protein, which was shown to be important for DC
differentiation and function. Our results suggest a novel regulatory
pathway for DC function that could contribute to the regulated balance
between immunity induction and self-tolerance
maintenance.
This article has been cited by other articles:
|
|
 |
|
  L. Klotz, S. Hucke, D. Thimm, S. Classen, A. Gaarz, J. Schultze, F. Edenhofer, C. Kurts, T. Klockgether, A. Limmer, et al. Increased Antigen Cross-Presentation but Impaired Cross-Priming after Activation of Peroxisome Proliferator-Activated Receptor {gamma} Is Mediated by Up-Regulation of B7H1 J. Immunol., July 1, 2009; 183(1): 129 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Marion-Letellier, P Dechelotte, M Iacucci, and S Ghosh Dietary modulation of peroxisome proliferator-activated receptor gamma Gut, April 1, 2009; 58(4): 586 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Perez-Cano, C. Ramirez-Santana, M. Molero-Luis, M. Castell, M. Rivero, C. Castellote, and A. Franch Mucosal IgA increase in rats by continuous CLA feeding during suckling and early infancy J. Lipid Res., March 1, 2009; 50(3): 467 - 476. [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]
|
|
|
|
 |
|
 A. Jaudszus, M. Krokowski, P. Mockel, Y. Darcan, A. Avagyan, P. Matricardi, G. Jahreis, and E. Hamelmann Cis-9,trans-11-Conjugated Linoleic Acid Inhibits Allergic Sensitization and Airway Inflammation via a PPAR{gamma}-Related Mechanism in Mice J. Nutr., July 1, 2008; 138(7): 1336 - 1342. [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]
|
|
|
|
 |
|
 R. Behshad, K. D. Cooper, and N. J. Korman A Retrospective Case Series Review of the Peroxisome Proliferator-Activated Receptor Ligand Rosiglitazone in the Treatment of Atopic Dermatitis Arch Dermatol, January 1, 2008; 144(1): 84 - 88. [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]
|
|
|
|
 |
|
 A. Nencioni, J. Beck, D. Werth, F. Grunebach, F. Patrone, A. Ballestrero, and P. Brossart Histone Deacetylase Inhibitors Affect Dendritic Cell Differentiation and Immunogenicity Clin. Cancer Res., July 1, 2007; 13(13): 3933 - 3941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, A. de Madariaga, and J. C. Domingo 9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development J. Immunol., May 15, 2007; 178(10): 6130 - 6139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Geyeregger, M. Zeyda, W. Bauer, E. Kriehuber, M. D. Saemann, G. J. Zlabinger, D. Maurer, and T. M. Stulnig Liver X receptors regulate dendritic cell phenotype and function through blocked induction of the actin-bundling protein fascin Blood, May 15, 2007; 109(10): 4288 - 4295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dubrac, P. Stoitzner, D. Pirkebner, A. Elentner, K. Schoonjans, J. Auwerx, S. Saeland, P. Hengster, P. Fritsch, N. Romani, et al. Peroxisome Proliferator-Activated Receptor-{alpha} Activation Inhibits Langerhans Cell Function J. Immunol., April 1, 2007; 178(7): 4362 - 4372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Klotz, I. Dani, F. Edenhofer, L. Nolden, B. Evert, B. Paul, W. Kolanus, T. Klockgether, P. Knolle, and L. Diehl Peroxisome Proliferator-Activated Receptor {gamma} Control of Dendritic Cell Function Contributes to Development of CD4+ T Cell Anergy J. Immunol., February 15, 2007; 178(4): 2122 - 2131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sandig, J. E. Pease, and I. Sabroe Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function J. Leukoc. Biol., February 1, 2007; 81(2): 372 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gogolak, B. Rethi, I. Szatmari, A. Lanyi, B. Dezso, L. Nagy, and E. Rajnavolgyi Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPAR{gamma} Blood, January 15, 2007; 109(2): 643 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Thurnher Lipids in dendritic cell biology: messengers, effectors, and antigens J. Leukoc. Biol., January 1, 2007; 81(1): 154 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Szatmari, A. Pap, R. Ruhl, J.-X. Ma, P. A. Illarionov, G. S. Besra, E. Rajnavolgyi, B. Dezso, and L. Nagy PPAR{gamma} controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells J. Exp. Med., October 2, 2006; 203(10): 2351 - 2362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Szatmari, G. Vamosi, P. Brazda, B. L. Balint, S. Benko, L. Szeles, V. Jeney, C. Ozvegy-Laczka, A. Szanto, E. Barta, et al. Peroxisome Proliferator-activated Receptor {gamma}-regulated ABCG2 Expression Confers Cytoprotection to Human Dendritic Cells J. Biol. Chem., August 18, 2006; 281(33): 23812 - 23823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nencioni, K. Schwarzenberg, K. M. Brauer, S. M. Schmidt, A. Ballestrero, F. Grunebach, and P. Brossart Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation Blood, July 15, 2006; 108(2): 551 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. August, C. Mueller, V. Weaver, T. A. Polanco, E. R. Walsh, and M. T. Cantorna Nutrients, Nuclear Receptors, Inflammation, Immunity Lipids, PPAR, and Allergic Asthma J. Nutr., March 1, 2006; 136(3): 695 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Appel, V. Mirakaj, A. Bringmann, M. M. Weck, F. Grunebach, and P. Brossart PPAR-{gamma} agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-{kappa}B pathways Blood, December 1, 2005; 106(12): 3888 - 3894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Armeanu, M. Bitzer, I. Smirnow, S. Bossow, S. Appel, G. Ungerechts, C. Bernloehr, W. J. Neubert, U. M. Lauer, and P. Brossart Severe Impairment of Dendritic Cell Allostimulatory Activity by Sendai Virus Vectors Is Overcome by Matrix Protein Gene Deletion J. Immunol., October 15, 2005; 175(8): 4971 - 4980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Appel, A. Rupf, M. M. Weck, O. Schoor, T. H. Brummendorf, T. Weinschenk, F. Grunebach, and P. Brossart Effects of Imatinib on Monocyte-Derived Dendritic Cells Are Mediated by Inhibition of Nuclear Factor-{kappa}B and Akt Signaling Pathways Clin. Cancer Res., March 1, 2005; 11(5): 1928 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, M. C. Rodriguez-Galan, J. J. Subleski, J. R. Ortaldo, D. L. Hodge, J.-M. Wang, O. Shimozato, D. A. Reynolds, and H. A. Young Peroxisome proliferator-activated receptor-{gamma} and its ligands attenuate biologic functions of human natural killer cells Blood, November 15, 2004; 104(10): 3276 - 3284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Skorokhod, M. Alessio, B. Mordmuller, P. Arese, and E. Schwarzer Hemozoin (Malarial Pigment) Inhibits Differentiation and Maturation of Human Monocyte-Derived Dendritic Cells: A Peroxisome Proliferator-Activated Receptor-{gamma}-Mediated Effect J. Immunol., September 15, 2004; 173(6): 4066 - 4074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nencioni and P. Brossart Cellular Immunotherapy with Dendritic Cells in Cancer: Current Status Stem Cells, July 1, 2004; 22(4): 501 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gehrmann, M. Brunner, K. Pfister, A. Reichle, E. Kremmer, and G. Multhoff Differential Up-Regulation of Cytosolic and Membrane-Bound Heat Shock Protein 70 in Tumor Cells by Anti-Inflammatory Drugs Clin. Cancer Res., May 15, 2004; 10(10): 3354 - 3364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Monaco and E. Paleolog Nuclear factor {kappa}B: a potential therapeutic target in atherosclerosis and thrombosis Cardiovasc Res, March 1, 2004; 61(4): 671 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Coutant, S. Agaugue, L. Perrin-Cocon, P. Andre, and V. Lotteau Sensing Environmental Lipids by Dendritic Cell Modulates Its Function J. Immunol., January 1, 2004; 172(1): 54 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hammad, H. J. de Heer, T. Soullie, V. Angeli, F. Trottein, H. C. Hoogsteden, and B. N. Lambrecht Activation of Peroxisome Proliferator-Activated Receptor-{gamma} in Dendritic Cells Inhibits the Development of Eosinophilic Airway Inflammation in a Mouse Model of Asthma Am. J. Pathol., January 1, 2004; 164(1): 263 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nencioni, K. Lauber, F. Grunebach, L. Van Parijs, C. Denzlinger, S. Wesselborg, and P. Brossart Cyclopentenone Prostaglandins Induce Lymphocyte Apoptosis by Activating the Mitochondrial Apoptosis Pathway Independent of External Death Receptor Signaling J. Immunol., November 15, 2003; 171(10): 5148 - 5156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gosset, F. Bureau, V. Angeli, M. Pichavant, C. Faveeuw, A.-B. Tonnel, and F. Trottein Prostaglandin D2 Affects the Maturation of Human Monocyte-Derived Dendritic Cells: Consequence on the Polarization of Naive Th Cells J. Immunol., May 15, 2003; 170(10): 4943 - 4952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Angeli, H. Hammad, B. Staels, M. Capron, B. N. Lambrecht, and F. Trottein Peroxisome Proliferator-Activated Receptor {gamma} Inhibits the Migration of Dendritic Cells: Consequences for the Immune Response J. Immunol., May 15, 2003; 170(10): 5295 - 5301. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
