Liver X Receptors Control IgE Expression in B Cells

Autor: Milena Milovanovic, Dennis Ernst, Margitta Worm, Kerstin Hilt, Björn Hartmann, Guido Heine, Anja Dahten
Rok vydání: 2009
Předmět:
Zdroj: The Journal of Immunology. 182:5276-5282
ISSN: 1550-6606
0022-1767
Popis: B lymphocytes play a fundamental role in the development of IgE-dependent allergic immune reactions. Upon appropriate activation, IgE class switch recombination is initiated in B cells, followed by terminal differentiation to IgE-secreting plasmablasts. This process is controlled by different nuclear receptors, including receptors for vitamin D, retinoids, and peroxisome proliferator-activated receptor-γ ligands. In this study, we show constitutive expression of the nuclear liver X receptor (LXR)α and LXRβ in peripheral human B cells. Activation of LXRs reduced secreted IgE (−68% ± 11) in CD40 and IL-4 activated B cells. The production of other isotypes, including IgG, IgM, IgA and B cell homeostatic parameters were not significantly altered by LXR activation. We identified inhibitory action of LXR activation on IgE production involving reduced phosphorylation of JNK and increased membrane CD23 expression (38% ± 11). The biological significance of our findings was validated by showing that systemic treatment of type I-sensitized BALB/c mice with LXR ligands reduced the serum concentrations of Ag-specific IgE in a dose-dependent manner (maximum, −52% ± 14). Thus, our data indicates that LXRs are involved in the control of IgE secretion by differentiating B cells.
Databáze: OpenAIRE