HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0804260v1 183/1/129    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Klotz, L. Articles by Burgdorf, S. PubMed PubMed Citation Articles by Klotz, L. Articles by Burgdorf, S.

Increased Antigen Cross-Presentation but Impaired Cross-Priming after Activation of Peroxisome Proliferator-Activated Receptor Is Mediated by Up-Regulation of B7H1¹

Luisa Klotz^2,3,, Stephanie Hucke^2,*, Dominik Thimm^*, Sabine Classen, Andrea Gaarz, Joachim Schultze, Frank Edenhofer, Christian Kurts^*, Thomas Klockgether, Andreas Limmer^*, Percy Knolle^* and Sven Burgdorf^3,*

^* Institutes of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany; and Laboratory for Genomics and Immunoregulation, Institute for Life and Medical Sciences, Institute of Reconstructive Neurobiology, Life and Brain Center, and Department of Neurology, University of Bonn, Bonn, Germany

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 (PPAR), 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 PPAR resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPAR 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 PPAR 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ L.K. was supported by Clinical Research Group Grant KFO177 and S.B. and C.K. by Collaborative Research Center Grant SFB645. Both grants were funded by the German Research Foundation.

² L.K. and S.H. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Luisa Klotz and Dr. Sven Burgdorf, Institutes of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. E-mail addresses: luisa.klotz{at}ukb.uni-bonn.de and Sven.Burgdorf{at}ukb.uni-bonn.de

⁴ Abbreviations used in this paper: DC, dendritic cell; MR, mannose receptor; PPAR, peroxisome proliferator-activated receptor ; Pio, pioglitazone; BM-DC, bone marrow-derived DC; MHC I/II, MHC class I/II; HTNCre, His-TAT-NLS-Cre; CPRG, chlorophenol red-β-D-galactopyranoside.

⁵ The online version of this article contains supplemental material.