Level of expression of IL-13R alpha 2 impacts receptor distribution and IL-13 signaling

• Published in: Journal of Immunology 2006-06, Vol.176 (12), p.7495-7501
• Main Authors: Daines, Michael O, Tabata, Yasuhiro, Walker, Bradley A, Chen, Weiguo, Warrier, Manoj R, Basu, Saswata, Hershey, Gurjit K Khurana
• Format: Article
• Language: English
• Subjects: Animals; Cell Membrane - genetics; Cell Membrane - immunology; Cell Membrane - metabolism; Clone Cells; Dose-Response Relationship, Immunologic; Humans; Interleukin-13 - antagonists & inhibitors; Interleukin-13 - metabolism; Interleukin-13 - physiology; Interleukin-13 Receptor alpha1 Subunit; Interleukin-4 - physiology; Intracellular Fluid - immunology; Intracellular Fluid - metabolism; Ligands; Mice; Mice, Inbred C3H; Protein Binding - genetics; Protein Binding - immunology; Receptors, IgE - biosynthesis; Receptors, Interleukin - biosynthesis; Receptors, Interleukin - chemistry; Receptors, Interleukin - genetics; Receptors, Interleukin - metabolism; Receptors, Interleukin-13; Signal Transduction - immunology; Solubility; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Transfection; U937 Cells
• ISSN: 0022-1767; 1365-2567
• DOI: 10.4049/jimmunol.176.12.7495

IL-13, a critical cytokine for allergic inflammation, exerts its effects through a complex receptor system including IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2. IL-4Ralpha and IL-13Ralpha1 form a heterodimeric signaling receptor for IL-13. In contrast, IL-13Ralpha2 binds IL-13 with high affinity but does not signal. IL-13Ralpha2 exists on the cell surface, intracellularly, and in soluble form, but no information is available regarding the relative distributions of IL-13Ralpha2 among these compartments, whether the compartments communicate, and how the relative expression levels impact IL-13 responses. Herein, we investigated the distribution of IL-13Ralpha2 in transfected and primary cells, and we evaluated how the total level of IL-13Ralpha2 expression impacted its distribution. Our results demonstrate that the distribution of IL-13Ralpha2 is independent of the overall level of expression. The majority of the IL-13Ralpha2 protein existed in intracellular pools. Surface IL-13Ralpha2 was continually released into the medium in a soluble form, yet surface expression remained constant supporting receptor trafficking to the cell surface. IL-13Ralpha2 inhibited IL-13 signaling proportionally to its level of expression, and this inhibition could be overcome with high concentrations of IL-13.