The Fc receptor common γ-chain (FcRγ) is a widely expressed adaptor bearing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. We found here that basophils lacking FcRγ developed normally and proliferated efficiently in response to interleukin 3 (IL-3), but were severely impaired in IL-3-induced IL-4 production and in supporting T helper 2 cell differentiation. Through the transmembrane portion, FcRγ associated constitutively with the common β-chain of the IL-3 receptor and signaled via recruiting the kinase Syk. Retrovirus-mediated complementation revealed the essential role for the ITAM of FcRγ in IL-3 signal transduction. These results uncover a novel mechanism for FcRγ function to 'route' selective cytokine-triggered signals into the ITAM-mediated IL-4 production pathway.Hida et al.

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BackgroundBisphenol A (BPA) is a widespread endocrine-disrupting chemical that can affect humans and animals.ObjectivesWe investigated the effects of adult or prenatal exposure to BPA on T-helper (TH)1/TH2 immune responses and the mechanisms underlying these effects.MethodsTo evaluate the effects of exposure to BPA in adulthood, male Leishmania major–susceptible BALB/c and –resistant C57BL/6 mice were subcutaneously injected with 0.625, 1.25, 2.5, and 5 μmol BPA 1 week before being infected with L. major. To evaluate prenatal exposure, female mice were given BPA-containing drinking water at concentrations of 1, 10, and 100 nM for 2 weeks, then mated, and given BPA for another week. Male 10-week-old offspring were infected with L. major. Footpad swelling was assessed as a measure of the course of infection.ResultsMice exposed to BPA prenatally or in adulthood showed a dose-dependent increase in footpad swelling after being infected with L. major. Exposure to BPA in adulthood significantly promoted antigen-stimulated production of interleukin (IL)-4, IL-10, and IL-13 but not interferon-γ (IFN-γ). However, mice prenatally exposed to BPA showed increased production of not only IL-4 but also IFN-γ. The percentages of CD4+CD25+ cells were decreased in mice exposed to BPA either prenatally or in adulthood. Effects of prenatal BPA exposure were far more pronounced than effects of exposure in adulthood.ConclusionBPA promotes the development of TH2 cells in adulthood and both TH1 and TH2 cells in prenatal stages by reducing the number of regulatory T cells.

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