Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134982
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Type: | Journal article |
Title: | Hhex Directly Represses BIM-Dependent Apoptosis to Promote NK Cell Development and Maintenance |
Author: | Goh, W. Scheer, S. Jackson, J.T. Hediyeh-Zadeh, S. Delconte, R.B. Schuster, I.S. Andoniou, C.E. Rautela, J. Degli-Esposti, M.A. Davis, M.J. McCormack, M.P. Nutt, S.L. Huntington, N.D. |
Citation: | Cell Reports, 2020; 33(3):108285-1-108285-20 |
Publisher: | Elsevier |
Issue Date: | 2020 |
ISSN: | 2211-1247 2211-1247 |
Statement of Responsibility: | Wilford Goh, Sebastian Scheer, Jacob T. Jackson, Soroor Hediyeh-Zadeh, Rebecca B. Delconte, Iona S. Schuster, Christopher E. Andoniou, Jai Rautela, Mariapia A. Degli-Esposti, Melissa J. Davis, Matthew P. McCormack, Stephen L. Nutt, and Nicholas D. Huntington |
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. |
Keywords: | NK cells; proliferation; survival; apoptosis; BIM; transcriptional regulation |
Rights: | © 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
DOI: | 10.1016/j.celrep.2020.108285 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1124784 http://purl.org/au-research/grants/nhmrc/GNT1066770 http://purl.org/au-research/grants/nhmrc/GNT1057852 http://purl.org/au-research/grants/nhmrc/GNT1124907 http://purl.org/au-research/grants/nhmrc/GNT1057812 http://purl.org/au-research/grants/nhmrc/GNT1049407 http://purl.org/au-research/grants/nhmrc/GNT1027472 http://purl.org/au-research/grants/nhmrc/GNT1184615 http://purl.org/au-research/grants/nhmrc/GNT1195296 http://purl.org/au-research/grants/nhmrc/GNT1155342 http://purl.org/au-research/grants/nhmrc/GNT1119298 |
Published version: | http://dx.doi.org/10.1016/j.celrep.2020.108285 |
Appears in Collections: | Molecular and Biomedical Science publications |
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hdl_134982.pdf | 3.01 MB | Adobe PDF | View/Open |
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