Hhex directly represses BIM-dependent apoptosis to promote NK cell development and maintenance
- Author(s)
- Goh, W; Scheer, S; Jackson, JT; Hediyeh-Zadeh, S; Delconte, RB; Schuster, IS; Andoniou, CE; Rautela, J; Degli-Esposti, MA; Davis, MJ; McCormack, MP; Nutt, SL; Huntington, ND;
- Details
- Publication Year 2020-10-20,Volume 33,Issue #3,Page 108285
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- Abstract
- Hhex encodes a homeobox transcriptional regulator important for embryonic development and hematopoiesis. Hhex is highly expressed in NK cells, and its germline deletion results in significant defects in lymphoid development, including NK cells. To determine if Hhex is intrinsically required throughout NK cell development or for NK cell function, we generate mice that specifically lack Hhex in NK cells. NK cell frequency is dramatically reduced, while NK cell differentiation, IL-15 responsiveness, and function at the cellular level remain largely normal in the absence of Hhex. Increased IL-15 availability fails to fully reverse NK lymphopenia following conditional Hhex deletion, suggesting that Hhex regulates developmental pathways extrinsic to those dependent on IL-15. Gene expression and functional genetic approaches reveal that Hhex regulates NK cell survival by directly binding Bcl2l11 (Bim) and repressing expression of this key apoptotic mediator. These data implicate Hhex as a transcriptional regulator of NK cell homeostasis and immunity.
- Publisher
- Cell Press
- Keywords
- Bim; NK cells; apoptosis; proliferation; survival; transcriptional regulation;
- Research Division(s)
- Immunology; Bioinformatics
- PubMed ID
- 33086067
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2020.108285
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2020.108285- Terms of Use/Rights Notice
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Creation Date: 2021-02-01 12:05:23
Last Modified: 2021-03-02 10:48:25