Cutting Edge: Inhibition of the retinoid X receptor (RXR) blocks T helper 2 differentiation and prevents allergic lung inflammation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Roland GrenninglohPaola Panina-Bordignon

Abstract

Among the many factors regulating Th cell differentiation, some nuclear hormone receptors are emerging as important players. The retinoid X receptor (RXR) functions as heterodimerization partner for a variety of nuclear hormone receptors. We show in this study that RXR is critical for Th2-mediated immunity. An RXR antagonist inhibited Th2 differentiation, resulting in reduced production of IL-4, IL-10, and IL-13, whereas IFN-gamma production was enhanced. This effect was dependent on the presence of APCs. In addition, IL-5 production was blocked directly in Th cells. In vivo, inhibition of RXR prevented experimentally induced allergic lung inflammation. Th1-mediated inflammation was not affected. Its specific role in Th2-mediated inflammation makes RXR a promising target for the development of therapies against diseases such as allergic asthma and atopic dermatitis.

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Citations

Nov 22, 2007·The Journal of Nutrition·Marielle MaretMarina Pretolani
Sep 16, 2006·American Journal of Respiratory and Critical Care Medicine·Maisa JaradatAnton M Jetten
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gertrud U SchusterCharles B Stephensen
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Nov 1, 2017·PloS One·Elena Marcos-VadilloMaría Isidoro-García
Feb 13, 2021·Frontiers in Immunology·Drishti Tiwari, Pawan Gupta
Dec 8, 2011·ACS Medicinal Chemistry Letters·Mariko NakayamaHiroki Kakuta

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