The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation Journal Article
| Authors: | Gordon, S. M.; Chaix, J.; Rupp, L. J.; Wu, J.; Madera, S.; Sun, J. C.; Lindsten, T.; Reiner, S. L. |
| Article Title: | The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation |
| Abstract: | 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. © 2012 Elsevier Inc. |
| Keywords: | controlled study; protein expression; gene deletion; nonhuman; flow cytometry; protein localization; cell proliferation; protein analysis; animal cell; mouse; phenotype; animals; mice; mice, knockout; animal tissue; cell cycle; reverse transcription polymerase chain reaction; cell maturation; embryo; protein stability; genotype; cell differentiation; cell lineage; gamma interferon; tumor necrosis factor related apoptosis inducing ligand; natural killer cell; killer cells, natural; cell cycle checkpoint; cytokine production; down regulation; fetus; transcription factor t bet; t box transcription factor; chemokine receptor cxcr3; models, immunological; extramedullary hematopoiesis; eomesodermin; chemokine receptor cxcr6; t-box domain proteins; real-time polymerase chain reaction; alpha2 integrin |
| Journal Title: | Immunity |
| Volume: | 36 |
| Issue: | 1 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2012-01-27 |
| Start Page: | 55 |
| End Page: | 67 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2011.11.016 |
| PROVIDER: | scopus |
| PUBMED: | 22261438 |
| PMCID: | PMC3381976 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2012" - "CODEN: IUNIE" - "Source: Scopus" |
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