Level of expression of IL-13Rα2 impacts receptor distribution and IL-13 signaling

IL-13, a critical cytokine for allergic inflammation, exerts its effects through a complex receptor system including IL-4R alpha, IL-13R alpha 1, and IL-13R alpha 2. IL-4R alpha and IL-13R alpha 1 form a heterodimeric signaling receptor for IL-13. In contrast, IL-13Ra2 binds IL-13 with high affinity but does not signal. IL-13R alpha 2 exists on the cell surface, intracellularly, and in soluble form, but no information is available regarding the relative distributions of IL-13R alpha 2 among these compartments, whether the compartments communicate, and how the relative expression levels impact IL-13 responses. Herein, we investigated the distribution of IL-13R alpha 2 in transfected and primary cells, and we evaluated how the total level of IL-13Ra2 expression impacted its distribution. Our results demonstrate that the distribution of IL-13R alpha 2 is independent of the overall level of expression. The majority of the IL-13R alpha 2 protein existed in intracellular pools. Surface IL-13R alpha 2 was continually released into the medium in a soluble form, yet surface expression remained constant supporting receptor trafficking to the cell surface. IL-13Ra2 inhibited IL-13 signaling proportionally to its level of expression, and this inhibition could be overcome with high concentrations of IL-13.