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The ubiquitin-editing enzyme A20 controls NK cell homeostasis through regulation of mTOR activity and TNF
| Content Provider | Scilit |
|---|---|
| Author | Vetters, Jessica Helden, Mary J. Van Wahlen, Sigrid Tavernier, Simon J. Martens, Arne Fayazpour, Farzaneh Vergote, Karl Vanheerswynghels, Manon Deswarte, Kim Moorleghem, Justine Van Prijck, Sofie De Takahashi, Nozomi Vandenabeele, Peter Boon, Louis Loo, Geert Van Vivier, Eric Lambrecht, Bart N. Janssens, Sophie |
| Copyright Year | 2019 |
| Description | The ubiquitin-editing enzyme A20 is a well-known regulator of immune cell function and homeostasis. In addition, A20 protects cells from death in an ill-defined manner. While most studies focus on its role in the TNF-receptor complex, we here identify a novel component in the A20-mediated decision between life and death. Loss of A20 in NK cells led to spontaneous NK cell death and severe NK cell lymphopenia. The few remaining NK cells showed an immature, hyperactivated phenotype, hallmarked by the basal release of cytokines and cytotoxic molecules. NK-A20−/− cells were hypersensitive to TNF-induced cell death and could be rescued, at least partially, by a combined deficiency with TNF. Unexpectedly, rapamycin, a well-established inhibitor of mTOR, also strongly protected NK-A20−/− cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. This study therefore maps A20 as a crucial regulator of mTOR signaling and underscores the need for a tightly balanced mTOR pathway in NK cell homeostasis. |
| Related Links | https://rupress.org/jem/article-pdf/216/9/2010/871241/jem_20182164.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719426/pdf https://rupress.org/jem/article-pdf/216/9/2010/847035/jem_20182164.pdf |
| Ending Page | 2023 |
| Page Count | 14 |
| Starting Page | 2010 |
| DOI | 10.1084/jem.20182164 |
| Journal | The Journal of experimental medicine |
| Issue Number | 9 |
| Volume Number | 216 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2019-09-02 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Cell Death Editing Regulator Tnf Ubiquitin Nk Cell A20 Mtor Activity Journal: The Journal of experimental medicine (Vol- 216, Issue- 9) |
| Content Type | Text |
