Cutting Edge: Inhibition of the retinoid X receptor (RXR) blocks T helper 2 differentiation and prevents allergic lung inflammation.
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.
Grenningloh
Roland
R
Bioxell SpA, Milan, Italy. rgrenningloh@rics.bwh.harvard.edu
Gho
Andrea
A
di Lucia
Pietro
P
Klaus
Michael
M
Bollag
Werner
W
Ho
I-Cheng
IC
Sinigaglia
Francesco
F
Panina-Bordignon
Paola
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D047488:Retinoid X Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects*
D015848:Interleukin-5; D047488:Retinoid X Receptors; D018664:Interleukin-12; D007371:Interferon-gamma