Delta-like 4 differentially regulates murine CD4 T cell expansion via BMI1
BACKGROUND: Studies have shown that Notch is essential for the maintenance of a T cell Th2 phenotype in vivo. It has also been shown that Notch ligands have diverse functions during T cell activation. We chose to investigate the role of Notch ligands during the Th2 response.
PRINCIPAL FINDINGS: We studied the relationship of two Notch ligands, delta-like 4 and jagged-1, to T cell proliferation in C57 Bl/6 mice. Our findings indicate that jagged-1 does not affect the rate of T cell proliferation in any subset examined. However, delta-like 4 causes an increase in the expansion of Th2 memory cells and a decrease in effector cell proliferation. Our in vivo studies indicate that the Notch system is dynamically regulated, and that blocking one Notch ligand increases the effective concentration of other Notch ligands, thus altering the response. Examination of genes related to the Notch pathway revealed that the Notch receptors were increased in memory T cells. Expression of BMI1, a gene involved in T cell proliferation, was also higher in memory T cells. Further experiments demonstrated that Notch directly regulates the expression of the BMI1 gene in T cells and may govern T cell proliferation through this pathway.
CONCLUSIONS: From these experiments we can make several novel conclusions about the role of Notch ligands in T cell biology. The first is that delta-like 4 suppresses effector cell proliferation and enhances Th2 memory cell proliferation. The second is that blocking one Notch ligand in vivo effectively increases the concentration of other Notch ligands, which can then alter the response.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
PloS one - 5(2010), 8 vom: 17. Aug., Seite e12172 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schaller, Matthew A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.11.2010 Date Revised 20.10.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0012172 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM20126899X |
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| 100 | 1 | |a Schaller, Matthew A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Delta-like 4 differentially regulates murine CD4 T cell expansion via BMI1 |
| 264 | 1 | |c 2010 | |
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| 500 | |a Date Completed 04.11.2010 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Studies have shown that Notch is essential for the maintenance of a T cell Th2 phenotype in vivo. It has also been shown that Notch ligands have diverse functions during T cell activation. We chose to investigate the role of Notch ligands during the Th2 response | ||
| 520 | |a PRINCIPAL FINDINGS: We studied the relationship of two Notch ligands, delta-like 4 and jagged-1, to T cell proliferation in C57 Bl/6 mice. Our findings indicate that jagged-1 does not affect the rate of T cell proliferation in any subset examined. However, delta-like 4 causes an increase in the expansion of Th2 memory cells and a decrease in effector cell proliferation. Our in vivo studies indicate that the Notch system is dynamically regulated, and that blocking one Notch ligand increases the effective concentration of other Notch ligands, thus altering the response. Examination of genes related to the Notch pathway revealed that the Notch receptors were increased in memory T cells. Expression of BMI1, a gene involved in T cell proliferation, was also higher in memory T cells. Further experiments demonstrated that Notch directly regulates the expression of the BMI1 gene in T cells and may govern T cell proliferation through this pathway | ||
| 520 | |a CONCLUSIONS: From these experiments we can make several novel conclusions about the role of Notch ligands in T cell biology. The first is that delta-like 4 suppresses effector cell proliferation and enhances Th2 memory cell proliferation. The second is that blocking one Notch ligand in vivo effectively increases the concentration of other Notch ligands, which can then alter the response | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Bmi1 protein, mouse |2 NLM | |
| 650 | 7 | |a Calcium-Binding Proteins |2 NLM | |
| 650 | 7 | |a DLL4 protein, mouse |2 NLM | |
| 650 | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a JAG1 protein, human |2 NLM | |
| 650 | 7 | |a Jag1 protein, mouse |2 NLM | |
| 650 | 7 | |a Jagged-1 Protein |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Notch |2 NLM | |
| 650 | 7 | |a Repressor Proteins |2 NLM | |
| 650 | 7 | |a Serrate-Jagged Proteins |2 NLM | |
| 650 | 7 | |a Polycomb Repressive Complex 1 |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 700 | 1 | |a Logue, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Mukherjee, Sumanta |e verfasserin |4 aut | |
| 700 | 1 | |a Lindell, Dennis M |e verfasserin |4 aut | |
| 700 | 1 | |a Coelho, Ana Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Lincoln, Pamela |e verfasserin |4 aut | |
| 700 | 1 | |a Carson, William F |c 4th |e verfasserin |4 aut | |
| 700 | 1 | |a Ito, Toshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Cavassani, Karen A |e verfasserin |4 aut | |
| 700 | 1 | |a Chensue, Stephen W |e verfasserin |4 aut | |
| 700 | 1 | |a Hogaboam, Cory M |e verfasserin |4 aut | |
| 700 | 1 | |a Lukacs, Nicholas W |e verfasserin |4 aut | |
| 700 | 1 | |a Kunkel, Steven L |e verfasserin |4 aut | |
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