Mouse macrophage development in the absence of the common gamma chain: Defining receptor complexes responsible for IL-4 and IL-13 signaling

The common gamma chain (gamma(c)) forms a critical component of the receptors for interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed gamma(c)-deficient mice to define a role for gamma(c) signaling in the development and function of the macrophage lineage. No major differences in absolute cell numbers, cell surface phenotype, or in vitro function of gamma(c)(-) compared to gamma(c)(+) macrophages were observed. We therefore conclude that signaling through the gamma(c) chain is not essential for the differentiation of mouse macrophages. Although B and T cells require gamma(c) for IL-4 responses, IL-4 up-regulated major histocompatibility class II molecules and inhibited nitric oxide production from gamma(c)(-) macrophages following stimulation with lipopolysaccharide and interferon-gamma. gamma(c)(-) macrophages could also respond to IL-13, consistent with the model of a type II IL-4 receptor alpha/IL-13R which can function in the absence of gamma(c). Both IL-4 and IL-13 responses could be completely inhibited with the mouse IL-4 antagonist QY, suggesting that all of the observed IL-13 responses pass through the type II receptor, making it the primary signaling receptor complex for IL-13 in mouse macrophages.