T-box transcription factors Eomes and T-bet regulate primary human NK cell IFNγ response and in vivo persistence

T-box transcription factors (TF) Eomes and T-bet are vital for NK cell development. However, their role in mature NK cell homeostasis and function remains unclear. Recently we reported that Eomes regulates mouse NK cell cytotoxicity and stage-specific survival using an NK-specific, tamoxifen-inducib...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.111-111.21
Main Authors: Wong, Pamela, Chang, Lily, Neal, Carly C, Wagner, Julia A, Berrien-Elliott, Melissa M, Cubitt, Celia C, Tran, Jennifer, Marsala, Lynne, Schappe, Timothy, Fehniger, Todd A
Format: Article
Language:English
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Summary:T-box transcription factors (TF) Eomes and T-bet are vital for NK cell development. However, their role in mature NK cell homeostasis and function remains unclear. Recently we reported that Eomes regulates mouse NK cell cytotoxicity and stage-specific survival using an NK-specific, tamoxifen-inducible Eomes KO model. However, the role of Eomes and T-bet have not been investigated in primary human NK (hNK) cell biology using genetic loss-of-function approaches. We hypothesized that these TFs play a critical role in maintaining NK cell functional molecular programs. Here we used CRISPR-Cas9 to genetically delete Eomes and T-bet expression in primary hNK cells. In vitro stimulation assays revealed that IFNγ response is impaired in CD56bright NK cells only when Eomes is deleted (p
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.206.Supp.111.21