Dendritic Cell Immunogenicity Is Regulated by Peroxisome Proliferator-Activated Receptor γ
- 1 August 2002
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 169 (3), 1228-1235
- https://doi.org/10.4049/jimmunol.169.3.1228
Abstract
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 gamma (PPAR-gamma), which has anti-inflammatory properties, redirects DC toward a less stimulatory mode. We show that activation of PPAR-gamma during DC differentiation profoundly affects the expression of costimulatory molecules and of the DC hallmarker CD1a. PPAR-gamma 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-gamma activators. Moreover, activation of PPAR-gamma 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.Keywords
This publication has 48 references indexed in Scilit:
- Efficient Presentation of Soluble Antigen by Cultured Human Dendritic Cells Is Maintained by Granulocyte/Macrophage Colony-stimulating Factor Plus Interleukin 4 and Downregulated by Tumor Necrosis Factor alphaThe Journal of Immunology, 2018
- Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in VivoThe Journal of Experimental Medicine, 2001
- Peroxisome proliferator‐activated receptor γ activators inhibit interleukin‐12 production in murine dendritic cellsFEBS Letters, 2000
- Oxidized Low Density Lipoprotein Inhibits Interleukin-12 Production in Lipopolysaccharide-activated Mouse Macrophages via Direct Interactions between Peroxisome Proliferator-activated Receptor-γ and Nuclear Factor-κBOnline Journal of Public Health Informatics, 2000
- The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic CellsThe Journal of Experimental Medicine, 2000
- Differential Expression of the Transcription Factor NF-κB during Human Mononuclear Phagocyte Differentiation to Macrophages and Dendritic CellsBiochemical and Biophysical Research Communications, 2000
- Peroxisome Proliferator-Activated Receptors: Nuclear Control of MetabolismEndocrine Reviews, 1999
- Selective activation of Fas/Fas ligand-mediated cytotoxicity by a self peptide.The Journal of Experimental Medicine, 1996
- Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factorCell, 1994
- GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cellsNature, 1992