دورية أكاديمية
أعرض في EDS

Hhex Directly Represses BIM-Dependent Apoptosis to Promote NK Cell Development and Maintenance.

التفاصيل البيبلوغرافية
العنوان: Hhex Directly Represses BIM-Dependent Apoptosis to Promote NK Cell Development and Maintenance.
المؤلفون: Goh W; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia., Scheer S; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia., Jackson JT; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia., Hediyeh-Zadeh S; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia., Delconte RB; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia., Schuster IS; Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, 6009, Australia; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia., Andoniou CE; Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, 6009, Australia; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia., Rautela J; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia; oNKo-Innate Pty Ltd., 27 Norwood Cres, Moonee Ponds, Victoria, 3039, Australia., Degli-Esposti MA; Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, 6009, Australia; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia., Davis MJ; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia; Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia., McCormack MP; The Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, 3004, Australia., Nutt SL; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia., Huntington ND; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia; oNKo-Innate Pty Ltd., 27 Norwood Cres, Moonee Ponds, Victoria, 3039, Australia. Electronic address: nicholas.huntington@monash.edu.au.
المصدر: Cell reports [Cell Rep] 2020 Oct 20; Vol. 33 (3), pp. 108285.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: Homeodomain Proteins/*metabolism , Killer Cells, Natural/*metabolism , Transcription Factors/*metabolism, Animals ; Apoptosis/genetics ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Cell Survival/physiology ; Female ; Gene Expression Regulation/genetics ; Hematopoiesis/genetics ; Homeodomain Proteins/genetics ; Homeodomain Proteins/physiology ; Interleukin-15/genetics ; Interleukin-15/immunology ; Killer Cells, Natural/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction/physiology ; Transcription Factors/genetics ; Transcription Factors/physiology
مستخلص: 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.
Competing Interests: Declaration of Interests N.D.H. and J.R. are cofounders and shareholders in oNKo-Innate. The other authors declared no competing interests.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: BIM; NK cells; apoptosis; proliferation; survival; transcriptional regulation
المشرفين على المادة: 0 (Hhex protein, mouse)
0 (Homeodomain Proteins)
0 (Interleukin-15)
0 (Transcription Factors)
تواريخ الأحداث: Date Created: 20201021 Date Completed: 20211018 Latest Revision: 20211018
رمز التحديث: 20240628
DOI: 10.1016/j.celrep.2020.108285
PMID: 33086067
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2020.108285