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T-BET and EOMES Acc...
T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells
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Kiekens, L (författare)
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Van Loocke, W (författare)
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Taveirne, S (författare)
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- Wahlen, S (författare)
- Karolinska Institutet
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Persyn, E (författare)
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Van Ammel, E (författare)
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De Vos, Z (författare)
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Matthys, P (författare)
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Van Nieuwerburgh, F (författare)
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Taghon, T (författare)
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Van Vlierberghe, P (författare)
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Vandekerckhove, B (författare)
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Leclercq, G (författare)
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(creator_code:org_t)
- 2021-09-24
- 2021
- Engelska.
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 732511-
- Relaterad länk:
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https://www.frontier...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.
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- Av författaren/redakt...
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Kiekens, L
-
Van Loocke, W
-
Taveirne, S
-
Wahlen, S
-
Persyn, E
-
Van Ammel, E
-
visa fler...
-
De Vos, Z
-
Matthys, P
-
Van Nieuwerburgh ...
-
Taghon, T
-
Van Vlierberghe, ...
-
Vandekerckhove, ...
-
Leclercq, G
-
visa färre...
- Artiklar i publikationen
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Frontiers in imm ...
- Av lärosätet
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Karolinska Institutet