Increased antigen cross-presentation but impaired cross-priming after activation of peroxisome proliferator-activated receptor γ is mediated by up-regulation of B7H1

Luisa Klotz, Stephanie Hucke, Dominik Thimm, Sabine Classen, Andrea Gaarz, Joachim Schultze, Frank Edenhofer, Christian Kurts, Thomas Klockgether, Andreas Limmer, Percy Knolle, Sven Burgdorf

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Dendritic cells are able to take up exogenous Ags and present Ag-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of APCs, has been demonstrated to target soluble Ags exclusively toward cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model Ag OVA. We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in dendritic cells induced up-regulation of the coinhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune responses, e.g., in T cell-mediated autoimmunity.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - 1 Jul 2009
Externally publishedYes

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