Level of expression of IL-13R alpha 2 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-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.
Daines
Michael O
MO
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children' Hospital Medical Center, OH 45229, USA
Tabata
Yasuhiro
Y
Walker
Bradley A
BA
Chen
Weiguo
W
Warrier
Manoj R
MR
Basu
Saswata
S
Hershey
Gurjit K Khurana
GK
D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000502:physiology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008809:Mice, Inbred C3H; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053660:Receptors, Interleukin-13; D015398:Signal Transduction / Q000276:immunology*; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D008024:Ligands; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4