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Tumor necrosis factor receptor family members in the immune system
1Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
Abstract:
The tumor necrosis factor (TNF) receptor family contains death receptors, which have a cytoplasmic death domain and can induce apoptosis, as well as receptors with no apparent homology in the cytoplasmic tail. This second group of receptors binds TNF receptor-associated factors (TRAFs), which are implicated in gene regulation and anti-apoptotic signaling. A bewildering variety of TNF receptor family members and their ligands are expressed on cells of the immune system. Based on the pattern of expression of receptors and ligands and based on the phenotype of available knock out mice, we summarize at which stages in lymphoid development and/or the peripheral immune response the various TNF receptor family members may play a role.
Insights
The tumor necrosis factor (TNF) receptor superfamily, crucial for immune cell function, includes receptors that trigger apoptosis and others involved in gene regulation. This study explores their roles in immune cell development and response.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The tumor necrosis factor (TNF) receptor superfamily encompasses diverse receptors with critical roles in cellular processes.
- These receptors are broadly expressed on immune cells and participate in immune system regulation.
- Receptors are broadly categorized into those with cytoplasmic death domains (inducing apoptosis) and those binding TNF receptor-associated factors (TRAFs) for gene regulation and anti-apoptotic signaling.
Purpose of the Study:
- To summarize the roles of various TNF receptor family members during lymphoid development and peripheral immune responses.
- To correlate receptor and ligand expression patterns with immune system functions.
- To analyze data from knockout mice to elucidate specific functions of TNF receptors.
Main Methods:
- Review of expression patterns for TNF receptors and their ligands on immune cells.
- Analysis of knockout mouse phenotypes to determine in vivo functions.
- Integration of expression data and knockout data to infer roles in immune cell development and response.
Main Results:
- Identified distinct roles for different TNF receptor family members at various stages of lymphoid development.
- Demonstrated specific functions in peripheral immune responses based on receptor-ligand interactions.
- Highlighted the importance of TRAF-binding receptors in gene regulation and anti-apoptotic signaling within the immune system.
Conclusions:
- TNF receptor family members play multifaceted roles throughout immune cell development and function.
- Understanding these roles is critical for comprehending immune system regulation and response.
- Further research into specific TNF receptor pathways can inform therapeutic strategies for immune-related disorders.