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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 06, 2018 |
| Title |
IL-10 induces a STAT3-dependent autoregulatory loop in Th2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Blimp-1 expression in T cells extinguishes the T follicular helper cell fate and drives terminal differentiation, but also limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in Th2 cells and the molecular basis of its actions. Herein, we report that STAT3 unexpectedly played a critical role in regulating Blimp-1 in Th2 cells. Furthermore, we found that the cytokine IL-10 acted directly on Th2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in Th2 cells, creating a strong autoregulatory loop that enhanced Blimp-1 expression. Increased Blimp-1 in T cells antagonized STAT5-regulated cell cycle and anti-apoptotic genes to limit cell expansion. These data elucidate the signals required for Blimp-1 expression in Th2 cells and reveal an unexpected mechanism of action of IL-10 in T cells, providing insights into the molecular underpinning by which Blimp-1 constrains T cell expansion to limit autoimmunity.
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| Overall design |
RNAseq of activated undifferentiated CD4 T cells with or without exogenous expression of Blimp-1.
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| Contributor(s) |
Poholek AC, Jankovic D, Villarino AV, Petermann F, Hettinga A, Shouval DS, Snapper SB, Kaech SM, Brooks SR, Vahedi G, Sher A, Kanno Y, O'Shea JJ |
| Citation(s) |
28713870 |
| Submission date |
Feb 05, 2018 |
| Last update date |
Mar 19, 2019 |
| Contact name |
Amanda Catherine Poholek |
| E-mail(s) |
poholeka@pitt.edu
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| Organization name |
University of Pittsburgh
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| Department |
Pediatrics
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| Street address |
4401 Penn Ave., Rangos Research Center 8129
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| City |
Pittsburgh |
| State/province |
Pennsylvania |
| ZIP/Postal code |
15224 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA433014 |
| SRA |
SRP132229 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110176_RNAseq_Blimp1RV_poholek.txt.gz |
714.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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