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Critical Reviews™ in Immunology

Impact factor: 3.857

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v23.i12.10
13 pages

Role of Peroxisome Proliferator-Activated Receptor g and Its Ligands in the Control of Immune Responses

Alessio Nencioni
Department of Internal Medicine, University of Genova, 16132 Genova, Italy; and Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Sebastian Wesselborg
Department of Internal Medicine I, University of Tubingen, Tubingen, Germany
Peter Brossart
Department of Hematology, Oncology and Immunology, University of Tübingen, Otfried Muller Str. 10; D-72076 Tübingen, Germany

ABSTRACT

To ensure that efficient immune responses against dangerous antigens are raised while tolerance to self molecules is preserved, the immune system tightly regulates activation and survival of its cellular compartments through mechanisms only partially characterized. In this context, recent evidence indicates a role in immunity of the nuclear receptor PPAR-g, which is upregulated in activated lymphocytes and in dendritic cells. Preliminary in vitro studies indicate that PPAR-g activation profoundly alters the immune properties of these cells, usually leading to the inhibition of immune responses. Naturally occurring PPAR-g ligands include the cyclopentenone prostaglandins of the J series, which are present in bone marrow, thymus, and secondary lymphatic tissues. The levels of these metabolites are increased in inflamed tissues, where they exert strong anti-inflammatory effects leading to resolution of inflammation and wound healing. Cyclopentenone prostaglandins activate both PPAR-g–dependent and PPAR-g–independent pathways, possess intrinsic proapoptotic potential and are direct inhibitors of NF-kB signaling. The relevance of these effects in vivo still awaits proper evaluation in humans. Some of the newly described regulatory pathways might eventually be exploited in the treatment of immune diseases by means of PPAR-g ligands, such as thiazolidinediones or prostaglandins.