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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Notch1 modulates mesenchymal stem cells mediated regulatory T-cell induction
Beatrice Del Papa1, Paolo Sportoletti, Debora Cecchini
1Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
European Journal of Immunology
|November 20, 2012
Summary
Mesenchymal stem cells (MSCs) induce regulatory T (Treg) cells via Notch1 signaling. This pathway activation is crucial for Treg cell differentiation and FOXP3 expression in human cells.
Area of Science:
- Immunology
- Cell Biology
- Stem Cell Research
Background:
- Regulatory T (Treg) cells are crucial for immune homeostasis.
- Mesenchymal stem cells (MSCs) have immunomodulatory properties, including Treg cell induction.
- The precise molecular mechanisms of MSC-mediated Treg cell induction require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms by which MSCs induce human Treg cells.
- To determine the role of Notch1 signaling in MSC-driven Treg cell differentiation.
- To identify downstream targets of Notch1 signaling in this context.
Main Methods:
- Co-culture of human CD4+ T cells with MSCs.
- Inhibition of Notch1 signaling using GSI-I and a Notch1 neutralizing antibody.
- Analysis of HES1 expression (Notch1 downstream target).
- Flow cytometry to quantify CD4+ CD25high FOXP3+ cells.
Main Results:
- Notch1 pathway activation was observed in CD4+ T cells co-cultured with MSCs.
- Inhibition of Notch1 signaling decreased HES1 expression and the percentage of induced Treg cells.
- FOXP3 was identified as a downstream target of Notch signaling in human cells.
- No crosstalk between Notch1 and TGF-β signaling was detected.
Conclusions:
- MSC-induced human Treg cell differentiation is mediated by the activation of the Notch1 signaling pathway.
- Notch1 signaling plays a critical role in the induction of FOXP3 expression in Treg cells.
- This study reveals a novel mechanism for MSC-mediated immune regulation.
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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...
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...
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