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| Status |
Public on Dec 31, 2022 |
| Title |
An XBP1s-PIM-2 positive feedback loop controls IL-15-mediated survival of natural killer cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
We previously reported that XBP1s, an essential transcription factor downstream of IL-15 and AKT signaling, controls cell survival and effector functions of human natural killer (NK) cells. However, the precise mechanisms remain unknown. In this study, by using XBP1 conditional knock-out mice, we found that XBP1s is critical for IL-15-mediated NK cell survival but not proliferation in vitro and in vivo. Mechanistically, XBP1s regulates homeostatic NK cell survival through targeting PIM-2, a critical anti-apoptotic gene, which in turn stabilizes XBP1s protein by phosphorylating it at Thr58. In addition, XBP1s enhances the effector functions and anti-tumor immunity of NK cells by recruiting T-bet to the promoter region of Ifng. Collectively, our findings identify a previously unknown mechanism by which IL-15–XBP1s signaling regulates the survival and effector functions of NK cells.
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| Overall design |
5 × 10E6 purified mouse primary NK cells from Il15TgXbp1f/f mice were pretreated with IL-15 (50 ng/ml) for 1 h. chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-Seq) was performed.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/36897958/
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| |
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| Contributor(s) |
Ma S, Yu J |
| Citation(s) |
36897958 |
| |
| Submission date |
Nov 22, 2022 |
| Last update date |
Apr 01, 2023 |
| Contact name |
Shoubao Ma |
| E-mail(s) |
shma@coh.org
|
| Phone |
6262182182
|
| Organization name |
City of Hope
|
| Street address |
1500 East Duarte Road
|
| City |
duarte |
| State/province |
California |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA904273 |
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