T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

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Fältnamn	Indikatorer	Metadata
000		03080naa a2200421 4500
001		oai:prod.swepub.kib.ki.se:147824147
003		SwePub
008		240124s2021 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1478241472 URI
024	7	a https://doi.org/10.3389/fimmu.2021.7325112 DOI
040		a (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Kiekens, L4 aut
245	1 0	a T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells
264		c 2021-09-24
264	1	b Frontiers Media SA,c 2021
506		a gratis
520		a 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.
700	1	a Van Loocke, W4 aut
700	1	a Taveirne, S4 aut
700	1	a Wahlen, Su Karolinska Institutet4 aut
700	1	a Persyn, E4 aut
700	1	a Van Ammel, E4 aut
700	1	a De Vos, Z4 aut
700	1	a Matthys, P4 aut
700	1	a Van Nieuwerburgh, F4 aut
700	1	a Taghon, T4 aut
700	1	a Van Vlierberghe, P4 aut
700	1	a Vandekerckhove, B4 aut
700	1	a Leclercq, G4 aut
710	2	a Karolinska Institutet4 org
773	0	t Frontiers in immunologyd : Frontiers Media SAg 12, s. 732511-q 12<732511-x 1664-3224
856	4	u https://www.frontiersin.org/articles/10.3389/fimmu.2021.732511/pdf
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:147824147
856	4 8	u https://doi.org/10.3389/fimmu.2021.732511

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Av författaren/redakt...: 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...

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Av lärosätet: Karolinska Institutet

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