A novel mechanism by which interferon-γ can regulate interleukin (IL)-13 responses. Evidence for intracellular stores of IL-13 receptor α-2 and their rapid mobilization by interferon-γ

Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor α-1 chain (IL-13Rα1) binds IL-13 with low affinity, but does not signal. However, when IL-13Rα1 combines with IL-4 receptor a (IL-4Rα), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13Rα2 alone binds IL-13 with high affinity, but does not signal and has been postulated to be a decoy receptor. Herein, we investigated the cellular localization of IL-13Rα2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13Rα2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN)-γ. Up-regulation of IL-13Rα2 surface expression in response to IFN-γ was rapid, did not require protein synthesis, and resulted in diminished IL-13 signaling. These results provide the first evidence that the IL-13Rα2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFN-α can regulate IL-13 responses.