A Novel Mechanism by Which Interferon- Can Regulate Interleukin (IL)-13 Responses EVIDENCE FOR INTRACELLULAR STORES OF IL-13 RECEPTOR -2 AND THEIR RAPID MOBILIZATION

Interleukin (IL)-13 mediates its activities via a complex receptor system. Interleukin-13 receptor -1 chain (IL-13R 1) binds IL-13 with low affinity, but does not signal. However, when IL-13R 1 combines with IL-4 receptor (IL-4R ), a signaling high affinity receptor complex for IL-13 is generated. In contrast, IL-13R 2 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-13R 2 and the regulation of its expression by confocal microscopy and flow cytometry in primary and cultured cells. Our results demonstrate that IL-13R 2 is largely an intracellular molecule, which is rapidly mobilized from intracellular stores following treatment with interferon (IFN). Up-regulation of IL-13R 2 surface expression in response to IFNwas rapid, did not require protein synthesis, and resulted in diminished IL-13 signaling. These results provide the first evidence that the IL-13R 2 is predominantly an intracellular molecule and demonstrate a novel mechanism by which IFNcan regulate IL-13 responses.