Document Detail


The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation.
MedLine Citation:
PMID:  22261438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-18
Journal Detail:
Title:  Immunity     Volume:  36     ISSN:  1097-4180     ISO Abbreviation:  Immunity     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-30     Completed Date:  2012-03-19     Revised Date:  2014-04-10    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  United States    
Other Details:
Languages:  eng     Pagination:  55-67     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
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:
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; R01 AI100874/AI/NIAID NIH HHS; T32 CA09140/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Eomes protein, mouse; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21
Comments/Corrections
Comment In:
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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