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Published on: September 28, 2018
Notch signaling regulates PD-1 expression during CD8(+) T-cell activation
Mélissa Mathieu1, Natacha Cotta-Grand, Jean-François Daudelin
1Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montréal, Quebec, Canada.
Immunology and Cell Biology
|October 17, 2012
Summary
The Notch signaling pathway regulates the expression of Programmed cell death 1 (PD-1) in activated CD8(+) T cells. This pathway inhibits PD-1 transcription, impacting T-cell function and exhaustion.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Programmed cell death 1 (PD-1) is a critical inhibitory receptor in T-cell regulation.
- Understanding PD-1 expression control during T-cell activation is crucial for immune response modulation.
- Previous research identified NFATc1, IRF9, and T-bet as regulators of PD-1 transcription.
Purpose of the Study:
- To investigate the role of the Notch signaling pathway in regulating PD-1 expression.
- To elucidate the molecular mechanisms by which Notch signaling influences PD-1 transcription in T cells.
Main Methods:
- Utilized specific inhibitors of the Notch signaling pathway.
- Assessed PD-1 expression levels in activated CD8(+) T cells.
- Performed chromatin immunoprecipitation (ChIP) assays to analyze promoter occupancy.
Main Results:
- Inhibition of Notch signaling led to decreased PD-1 expression.
- Notch pathway inhibition suppressed Pdcd1 (PD-1) gene transcription.
- ChIP assays confirmed the binding of RBPJk and Notch1 intracellular domain to the Pdcd1 promoter.
Conclusions:
- The Notch signaling pathway is a significant regulator of PD-1 expression in activated CD8(+) T cells.
- Notch signaling directly impacts Pdcd1 transcription through RBPJk-dependent mechanisms.
- Findings provide new insights into the molecular control of T-cell exhaustion and immune tolerance.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
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01:20The JAK-STAT Signaling Pathway
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