Your browser doesn't support javascript.
loading
Hhex Directly Represses BIM-Dependent Apoptosis to Promote NK Cell Development and Maintenance.
Goh, Wilford; Scheer, Sebastian; Jackson, Jacob T; Hediyeh-Zadeh, Soroor; Delconte, Rebecca B; Schuster, Iona S; Andoniou, Christopher E; Rautela, Jai; Degli-Esposti, Mariapia A; Davis, Melissa J; McCormack, Matthew P; Nutt, Stephen L; Huntington, Nicholas D.
Affiliation
  • 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, Biome
  • 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,
  • 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, Biome
Cell Rep ; 33(3): 108285, 2020 10 20.
Article in En | MEDLINE | ID: mdl-33086067
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.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Killer Cells, Natural / Homeodomain Proteins Limits: Animals Language: En Journal: Cell Rep Year: 2020 Document type: Article Affiliation country:
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Killer Cells, Natural / Homeodomain Proteins Limits: Animals Language: En Journal: Cell Rep Year: 2020 Document type: Article Affiliation country: