Dendritic cell immunogenicity is regulated by peroxisome proliferator-activated receptor γ

Alessio Nencioni, Frank Grünebach, Anke Zobywlaski, Claudio Denzlinger, Wolfram Brugger, Peter Brossart

Research output: Contribution to journalArticle

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 γ (PPAR-γ), which has anti-inflammatory properties, redirects DC toward a less stimulatory mode. We show that activation of PPAR-γ during DC differentiation profoundly affects the expression of costimulatory molecules and of the DC hallmarker CD1a. PPAR-γ 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-γ activators. Moreover, activation of PPAR-γ 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 ReIB 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.

Original languageEnglish
Pages (from-to)1228-1235
Number of pages8
JournalJournal of Immunology
Volume169
Issue number3
Publication statusPublished - Aug 1 2002

ASJC Scopus subject areas

  • Immunology

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    Nencioni, A., Grünebach, F., Zobywlaski, A., Denzlinger, C., Brugger, W., & Brossart, P. (2002). Dendritic cell immunogenicity is regulated by peroxisome proliferator-activated receptor γ. Journal of Immunology, 169(3), 1228-1235.