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Basal Signaling Suppresses RAG Genes during T Cell Development

View Article: PubMed Central

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Faced with all manner of potential threats in the form of billions of different viral, bacterial, and chemical pathogens, the mammalian immune system relies on a “safety in diversity” strategy for protection... But as Jeroen Roose, Arthur Weiss, and colleagues report, signaling pathways activated by bound TCRs appear to influence gene expression even in the absence of antigen or other receptor ligands, a process called ligand-independent signaling... These findings lend support to the notion that cellular signaling pathways regulated by surface receptors, like TCRs, exhibit a continuous low-level signaling (known as basal signaling) in the absence of a stimulus and that this continuous signaling, by influencing gene expression, has significant influence on cellular differentiation... RAG genes regulate the genetic recombination and ultimate cell surface expression of TCRs... Using chemical inhibitors and mutant human T cell lines deficient in critical signaling components involved in antigen receptor-dependent pathways, the researchers found that the loss of specific functions or specific proteins affected an unexpected set of target genes... Most importantly, these findings suggest that signaling pathways thought to be triggered only by ligated receptors can influence gene expression on their own... And it may be through this type of signaling that TCR pathways help regulate T cell development by repressing RAG gene activity... These basal signals, the researchers postulate, may in effect save the RAG expression machinery until recombination is called for... If RAG genes were expressed at the wrong time, they could cause inappropriate genetic recombination and create T cells that either lack function or attack healthy cells, as happens in immunodeficiency and autoimmune diseases... Elucidating the mechanisms and components of this basal pathway will contribute important insights into the development and function of the immune system.

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Basal signaling suppresses RAG gene
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pbio.0000063-g001: Basal signaling suppresses RAG gene


Basal Signaling Suppresses RAG Genes during T Cell Development
Basal signaling suppresses RAG gene
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC261897&req=5

pbio.0000063-g001: Basal signaling suppresses RAG gene

View Article: PubMed Central

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Faced with all manner of potential threats in the form of billions of different viral, bacterial, and chemical pathogens, the mammalian immune system relies on a “safety in diversity” strategy for protection... But as Jeroen Roose, Arthur Weiss, and colleagues report, signaling pathways activated by bound TCRs appear to influence gene expression even in the absence of antigen or other receptor ligands, a process called ligand-independent signaling... These findings lend support to the notion that cellular signaling pathways regulated by surface receptors, like TCRs, exhibit a continuous low-level signaling (known as basal signaling) in the absence of a stimulus and that this continuous signaling, by influencing gene expression, has significant influence on cellular differentiation... RAG genes regulate the genetic recombination and ultimate cell surface expression of TCRs... Using chemical inhibitors and mutant human T cell lines deficient in critical signaling components involved in antigen receptor-dependent pathways, the researchers found that the loss of specific functions or specific proteins affected an unexpected set of target genes... Most importantly, these findings suggest that signaling pathways thought to be triggered only by ligated receptors can influence gene expression on their own... And it may be through this type of signaling that TCR pathways help regulate T cell development by repressing RAG gene activity... These basal signals, the researchers postulate, may in effect save the RAG expression machinery until recombination is called for... If RAG genes were expressed at the wrong time, they could cause inappropriate genetic recombination and create T cells that either lack function or attack healthy cells, as happens in immunodeficiency and autoimmune diseases... Elucidating the mechanisms and components of this basal pathway will contribute important insights into the development and function of the immune system.

No MeSH data available.