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Series GSE39529 Query DataSets for GSE39529
Status Public on Oct 03, 2012
Title Foxp3 expression is required for the induction of therapeutic tissue tolerance
Organism Mus musculus
Experiment type Expression profiling by array
Summary CD4+Foxp3+ regulatory T cells (Treg) are essential for immune homeostasis and maintenance of self-tolerance. They are produced in the thymus and also generated de novo in the periphery in a TGFB dependent manner. Foxp3+ Treg are also required to achieve tolerance to transplanted tissues when induced by co-receptor or costimulation blockade. Using TCR transgenic mice to avoid issues of autoimmune pathology we show that Foxp3 expression is necessary and sufficient for tissue tolerance by coreceptor blockade. Moreover, the known need in tolerance induction for TGFB signalling to T cells, can wholly be explained by its role in induction of Foxp3, as such signalling proved dispensable for the suppressive process. We analysed the relative contribution of TGFB and Foxp3 on the transcriptome of TGFB induced Treg. TGFB elicited a large set of downregulated signature genes. The number of genes uniquely modulated due to the influence of Foxp3 alone was surprisingly limited. Retroviral conditional Foxp3 expression proved sufficient to confer transplant-suppressive potency on CD4+ T cells, and was lost once nuclear Foxp3 expression was extinguished. Thus despite the large genetic influence of TGFB exposure on iTreg the crucial Foxp3 influenced signature independent of TGFB is small. These data support a dual role for TGFB and Foxp3 in induced tolerance, where TGFB stimulates Foxp3 expression whose sustained expression is associated with acquisition of tolerance
 
Overall design 21 samples were analyzed. 5 replicates of Marilyn.Foxp3hCD2 activated (HY)(Untreated) and TGFB-induced (HYT) cells sorted as CD4+hCD2+ and CD4+hCD2- and 3 replicates of Marilyn.Foxp3-/- activated and TGFβ-experienced (but Foxp3-) cells sorted as CD4+CD2. Pairwise comparisons were generated for the Marilyn Foxp3hCD2 UT versus TGFB induced populations and also for the Marilyn Foxp3-/- UT versus the TGFB experienced cells sorted as CD4+CD2
 
Contributor(s) Madhiwalla S, Zhang M, Howie D
Citation(s) 22988034
Submission date Jul 20, 2012
Last update date Mar 06, 2018
Contact name Duncan Howie
E-mail(s) duncan.howie@googlemail.com
Phone 01865 275518
Organization name Genzyme Corporation/Sir William Dunn School of Pathology Oxford University
Street address 49 New York Avenue
City Framingham
State/province MA
ZIP/Postal code 01701
Country USA
 
Platforms (1)
GPL6096 [MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version]
Samples (21)
GSM970931 Marilyn.Foxp3hCD2 activated (HY)(Untreated) biological replicate 1
GSM970932 Marilyn.Foxp3hCD2 activated (HY)(Untreated) biological replicate 2
GSM970933 Marilyn.Foxp3hCD2 activated (HY)(Untreated) biological replicate 3
Relations
BioProject PRJNA171053

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39529_RAW.tar 492.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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