Supplementary Material for: The Interleukin-13 Receptor-α1 Chain Is Essential for Induction of the Alternative Macrophage Activation Pathway by IL-13 but Not IL-4

Macrophages coexpress both the interleukin (IL)-2Rγ chain (γ_c) and IL-13Rα1. These receptor chains can heterodimerize with IL-4Rα to form type I or type II IL-4 receptor complexes, respectively. We used macrophages derived from <i>Il2rg</i> and <i>Il13ra1</i> knockout (KO) mice to evaluate the requirements for these receptor chains for induction of the alternative macrophage activation (AMA) pathway by IL-4 and IL-13. Absence of γ_c significantly decreased activation of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by IL-4 was markedly reduced in γ_c KO macrophages, it was not abolished, indicating that IL-4 can still signal through type II IL-4 receptors via the IL-13Rα1 chain. IL-13 failed to activate STAT6 in macrophages derived from <i>Il13ra1</i> KO mice; however, these cells remained fully responsive to IL-4. The inability of IL-13 but not IL-4 to signal in <i>Il13ra1</i>^-/- macrophages correlated with the inability of IL-13 but not IL-4 to induce expression of genes such as <i>Arg1</i>,<i> Retnla </i>and<i> Ccl11</i> that are characteristically expressed by alternatively activated macrophages. In addition, IL-13 but not IL-4 failed to induce membrane fusion and giant cell formation by <i>Il13ra1</i> KO macrophages. These findings demonstrate that the IL-13Rα1 chain is essential for induction of the AMA pathway by IL-13 but not IL-4.