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Status |
Public on Feb 15, 2008 |
Title |
AKT regulates de novo induction of Foxp3 |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
The CD4+Foxp3+ regulatory T cells play an essential role in maintaining tolerance via their suppressive function on conventional T cells. The intracellular signaling pathways that regulate Foxp3 expression are largely unknown. In this study we describe a novel inhibitory role for AKT in regulating de novo induction of Foxp3 both in vivo and in vitro. A constitutively active allele of AKT significantly diminished TGF-รข induced Foxp3 induction via a rapamycin-sensitive pathway, establishing a role for the AKT-mTOR axis in Treg cells. Moreover, the observed impairment in Foxp3 induction was paralleled by a selective downmodulation of the imparted Treg transcriptional signature highlighting the importance of the balance of intracellular signals in Treg differentiation . Our results provide a basis for further elucidation of molecular mechanisms that regulate Foxp3 induction and identify AKT as an important negative regulator of this process. Keywords: Cell population comparison
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Overall design |
All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and three replicates were generated for all groups. RNA from 0.5-2.5 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.
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Contributor(s) |
Haxhinasto S, Mathis D, Benoist C |
Citation(s) |
18283119 |
Submission date |
Apr 24, 2007 |
Last update date |
Feb 11, 2019 |
Contact name |
CBDM Lab |
E-mail(s) |
cbdm@hms.harvard.edu
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Phone |
617-432-7747
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Organization name |
Harvard Medical School
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Department |
Microbiology and Immunobiology
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Lab |
CBDM
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Street address |
77 Avenue Louis Pasteur
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02215 |
Country |
USA |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (6)
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Relations |
BioProject |
PRJNA100163 |