| The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation. | |
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MedLine Citation:
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PMID: 22261438 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet. Conversely, maturation characterized by loss of constitutive TRAIL expression and induction of Ly49 receptor diversity and integrin CD49b (DX5(+)) required Eomes. Mature NK cells from which Eomes was deleted reverted to phenotypic immaturity if T-bet was present or downregulated NK lineage antigens if T-bet was absent, despite retaining expression of Ly49 receptors. Fetal and adult hepatic hematopoiesis restricted Eomes expression and limited NK development to the T-bet-dependent, immature stage, whereas medullary hematopoiesis permitted Eomes-dependent NK maturation in adult mice. These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis. |
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Authors:
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Scott M Gordon; Julie Chaix; Levi J Rupp; Junmin Wu; Sharline Madera; Joseph C Sun; Tullia Lindsten; Steven L Reiner |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-18 |
Journal Detail:
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Title: Immunity Volume: 36 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-01-30 Completed Date: 2012-03-19 Revised Date: 2013-05-15 |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 55-67 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / genetics* Cell Differentiation* Cell Lineage Flow Cytometry Gene Deletion Killer Cells, Natural / cytology*, immunology* Mice Mice, Knockout Models, Immunological Real-Time Polymerase Chain Reaction T-Box Domain Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI042370/AI/NIAID NIH HHS; AI061699/AI/NIAID NIH HHS; AI076458/AI/NIAID NIH HHS; R01 AI042370-14/AI/NIAID NIH HHS; R01 AI042370-15/AI/NIAID NIH HHS; R01 AI061699/AI/NIAID NIH HHS; R01 AI061699-07/AI/NIAID NIH HHS; R01 AI061699-08/AI/NIAID NIH HHS; R01 AI076458-04/AI/NIAID NIH HHS; R01 AI076458-05/AI/NIAID NIH HHS; T32 CA09140/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Eomes protein, mouse; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21 |
| Comments/Corrections | |
Comment In:
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Immunity. 2012 Jan 27;36(1):1-3
[PMID:
22284412
]
Nat Rev Immunol. 2012 Mar;12(3):150 [PMID: 22322319 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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