9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) ligand, exerts immunosuppressive effects on dendritic cells by RXR-dependent activation: Inhibition of peroxisome proliferator-activated receptor γ blocks some of the 9cRA activities, and precludes them to mature phenotype development

Fernando Zapata-Gonzalez, Félix Rueda, Jordi Petriz, Pere Domingo, Francesc Villarroya, Africa De Madariaga, Joan C. Domingo

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    Abstract

    At nanomolar range, 9-cis-retinoic acid (9cRA) was able to interfere in the normal differentiation process from human monocyte to immature dendritic cell (DC) and produced a switch in mature DCs to a less stimulatory mode than untreated cells. 9cRA-treated mature DCs secreted high levels of IL-10 with an IL-12 reduced production. The phenotypic alterations unleashed by 9cRA were similar but not identical to other specific retinoid X receptor (RXR) agonists and to those already reported for rosiglitazone, a PPARγ activator, on DCs. The simultaneous addition of 9cRA and rosiglitazone on DCs displayed additive effects. Moreover, addition to cultures of G W9662, a specific inhibitor of PPARγ, or the RXR pan-antagonist HX603, blocked these changes. All these results suggest an activation of PPARγ-RXR and other RXR containing dimers by 9cRA in DCs. Finally, both GW9662 and HX603 by themselves altered the maturation process unleashed by TNFα, poly(I:C) or LPS on human DCs further suggesting that the heterodimer PPARγ-RXR must fulfill a significant role in the physiological maturation process of these cells in addition to the repressing effects reported till now for this nuclear receptor. Copyright © 2007 by The American Association of Immunologists, Inc.
    Original languageEnglish
    Pages (from-to)6130-6139
    JournalJournal of Immunology
    Volume178
    Issue number10
    Publication statusPublished - 15 May 2007

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