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Status |
Public on Jan 09, 2016 |
Title |
Transmission of survival signals through Delta-like 1 on activated CD4+ T cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival by interacting with Notch ligands on adjacent cells. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remain unclear. In this report we demonstrate that the Notch ligand Dll1 on CD4+ T cells transduces signals required for the maintenance of activated CD4+ T cells without affecting Notch signaling in the same cells. T cell-specific Dll1-deficient (Dll1-/-) mice did not show any defect in T cell development in thymus or spleen. Co-transfer of CD4+ T cells from Dll1-/- and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1-/- mice compared with control cells. Dll1-/- mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1-/- mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data highlight Dll1 as an independent regulator of Notch-signaling for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses
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Overall design |
The mRNA expression in activated CD4+ T cells from mouse was obtained by DNA microarray analysis. These mRNA expression was compared.
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Contributor(s) |
Furukawa T, Yasutomo K, Horikawa H |
Citation missing |
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Submission date |
Jan 08, 2016 |
Last update date |
Feb 02, 2018 |
Contact name |
Takahiro Furukawa |
E-mail(s) |
ft1981tf@gmail.com
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Organization name |
Tokushima University
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Street address |
Kuramoto-Cho 2-50-1
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City |
Tokushima |
ZIP/Postal code |
7708503 |
Country |
Japan |
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Platforms (1) |
GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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Samples (3) |
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Relations |
BioProject |
PRJNA308329 |