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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 06, 2012 |
| Title |
Gene expression profiling of in vitro derived induced and natural FOXP3+ regulatory T cells and ex-iTreg cells in the mouse |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Induced Treg (iTreg) cells are essential for tolerance and can be used therapeutically, yet their stability in vivo and mechanisms of suppression are unresolved. Here, we used a treatment model of colitis to examine the role of autologous IL-10 in iTreg cell function. Mice treated with IL-10+/+ iTreg cells in combination with IL-10–/– natural Treg (nTreg) cells survived and gained weight, even though iTreg cells were numerically disadvantaged and comprised just ~20% of all Treg cells in treated mice. Notably, ~85% of the transferred iTreg cells lost Foxp3 expression (ex-iTreg) but retained a portion of the iTreg transcriptome which failed to limit their pathogenic potential. The TCR repertoires of iTreg and ex-iTreg cells exhibited almost no overlap, which indicates that the two populations are clonally unrelated and maintained by different selective pressures. These data demonstrate a potent and critical role for iTreg cell produced IL-10 that can supplant the IL-10 produced by nTreg cells and compensate for the inherent instability of the iTreg population.
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| Overall design |
BALB/c Rag1-/- mice were treated with 500,00 WT nTreg cells plus 500,000 WT in-vitro-derived iTreg cells. After 125 days cells were sorted by flow cytometry from spleens and mesenteric lymph nodes from 14 treated mice. EGFP+ Thy1.1+ iTreg cells, EGFP+ Thy1.1– nTreg cells, and EGFP–Thy1.1+ ex-iTreg cells were pooled and used to generate total RNA for each iTreg, nTreg, and ex-iTreg array set, which was labeled and hybridized to Affymetrix 430 2.0 GeneChips in accordance to the manufacturer’s protocol. Two sets of arrays were performed, and the results were averaged. Both iTreg and nTreg array sets were compared to a) naïve CD4+EGFP– Tconv cells from Foxp3EGFP. The subset of probe sets whose expression increased or decreased by twofold or more relative to Tconv cells as a common standard was identified and used for further analysis.
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| Contributor(s) |
Schmitt EG, Haribhai D, Williams JB, Aggarwal P, Jia S, Yan K, Lorier R, Turner A, Jennifer Z, Simpson P, Salzman N, Hessner MJ, Broeckel U, Wiliams CB |
| Citation(s) |
23125413 |
| Submission date |
Feb 03, 2012 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Martin Hessner |
| E-mail(s) |
mhessner@mcw.edu
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| Organization name |
Medical College of Wisconsin
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| Department |
Pediatrics
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| Lab |
Max McGee National Research Center for Juvenile Diabetes
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| Street address |
8701 Watertown Plank Road
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| City |
Milwaukee |
| State/province |
WI |
| ZIP/Postal code |
53226 |
| 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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| GSM870351 |
Mouse invivo nTreg cells, replicate pool 1 |
| GSM870352 |
Mouse invivo nTreg cells, replicate pool 2 |
| GSM870353 |
Mouse stable invitro iTreg cells, replicate pool 1 |
| GSM870354 |
Mouse stable invitro iTreg cells, replicate pool 2 |
| GSM870355 |
Mouse ex-iTreg cells, replicate pool 1 |
| GSM870356 |
Mouse ex-iTreg cells, replicate pool 2 |
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| Relations |
| BioProject |
PRJNA152273 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35543_RAW.tar |
20.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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