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 (γc)
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 Il2rg and Il13ra1 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 γc significantly decreased activation
of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by
IL-4 was markedly reduced in γc 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 Il13ra1 KO mice; however, these cells remained fully responsive to IL-4. The inability of IL-13 but not IL-4 to signal in Il13ra1-/- macrophages correlated with the inability of IL-13 but not IL-4 to induce expression of genes such as Arg1, Retnla and Ccl11
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 Il13ra1 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.