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| Status |
Public on Nov 01, 2015 |
| Title |
IL-27 stimulation in Foxp3+ Tregs improves suppressive function and therapeutic efficacy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine.
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| Overall design |
FACS purified Foxp3+ Tregs were stimulated in the presence of media or IL-27 to compare IL-27 induced gene profiles. Four samples (media stimulated or IL-27-stimulated) were collected from four independent experiments. Genes altered by IL-27 treatment were compared to those of media stimulated Tregs.
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| Contributor(s) |
Min B, Do J, Sanogo YO |
| Citation(s) |
26013006 |
| |
| Submission date |
Nov 19, 2014 |
| Last update date |
Mar 30, 2020 |
| Contact name |
Yibayiri Osee Sanogo |
| Organization name |
Cleveland Clinic Foundation
|
| Department |
Genomics Core
|
| Street address |
9500 S Euclid Ave
|
| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44195 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19441 |
Illumina mouseref-8_v2_0_r3 expression beadchip |
|
| Samples (8)
|
| GSM1550129 |
Tregs stimulated in the presence of media. Replicate #1 |
| GSM1550130 |
Tregs stimulated in the presence of IL-27. Replicate #1 |
| GSM1550131 |
Tregs stimulated in the presence of media. Replicate #2 |
| GSM1550132 |
Tregs stimulated in the presence of IL-27. Replicate #2 |
| GSM1550133 |
Tregs stimulated in the presence of media. Replicate #3 |
| GSM1550134 |
Tregs stimulated in the presence of IL-27. Replicate #3 |
| GSM1550135 |
Tregs stimulated in the presence of media. Replicate #4 |
| GSM1550136 |
Tregs stimulated in the presence of IL-27. Replicate #4 |
|
| Relations |
| BioProject |
PRJNA267833 |
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