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Cutting Edge: Inhibition of the Retinoid X Receptor (RXR) Blocks T Helper 2 Differentiation and Prevents Allergic Lung Inflammation

Roland Grenningloh^1,*,, Andrea Gho^*, Pietro di Lucia^*, Michael Klaus^2,, Werner Bollag^3,, I-Cheng Ho, Francesco Sinigaglia^* and Paola Panina-Bordignon^*

^* Bioxell SpA, Milan, Italy; Basilea Pharmaceutica AG, Basel, Switzerland; and Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston MA 02115

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- 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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