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Mouse macrophage development in the absence of the common gamma chain: defining receptor complexes responsible for
A Andersson1, S M Grunewald, A Duschl
1INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
Abstract:
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 OY, 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.
Insights
Signaling through the common gamma chain (gamma c) is not essential for mouse macrophage development. However, gamma c- macrophages show distinct responses to interleukins (IL)-4 and IL-13.
Area of Science:
- Immunology
- Cell Biology
Background:
- The common gamma chain (gamma c) is a shared receptor component for multiple interleukins (ILs), including IL-2, IL-4, IL-7, IL-9, and IL-15.
- Gamma c signaling is crucial for lymphocyte development and function, but its role in myeloid cells like macrophages is less understood.
Purpose of the Study:
- To investigate the role of gamma c signaling in the development and function of macrophages.
- To determine if gamma c is essential for macrophage differentiation and response to specific interleukins.
Main Methods:
- Analysis of gamma c-deficient (gamma c-) and wild-type (gamma c+) mice.
- Assessment of macrophage cell numbers, surface phenotype, and in vitro function.
- Evaluation of IL-4 and IL-13 responses in gamma c- macrophages.
Main Results:
- No significant differences were observed in the development, phenotype, or basic in vitro function of gamma c- macrophages compared to gamma c+ macrophages.
- Gamma c- macrophages exhibited IL-4-mediated upregulation of major histocompatibility class II molecules and inhibition of nitric oxide production.
- Macrophages deficient in gamma c responded to IL-13, suggesting the involvement of an alternative receptor complex.
Conclusions:
- Gamma c signaling is not essential for the differentiation of mouse macrophages.
- Macrophages utilize alternative signaling pathways, such as the type II IL-4 receptor alpha/IL-13R, for responses to IL-4 and IL-13.
- The type II receptor appears to be the primary signaling complex for IL-13 in mouse macrophages.