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Publication : Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1.

First Author  Ramirez K Year  2012
Journal  Immunity Volume  36
Issue  6 Pages  921-32
PubMed ID  22608498 Mgi Jnum  J:187317
Mgi Id  MGI:5436189 Doi  10.1016/j.immuni.2012.04.006
Citation  Ramirez K, et al. (2012) Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1. Immunity 36(6):921-32
abstractText  Multiple transcription factors guide the development of mature functional natural killer (NK) cells, yet little is known about their function. We used global gene expression and genome-wide binding analyses combined with developmental and functional studies to unveil three roles for the ETS1 transcription factor in NK cells. ETS1 functions at the earliest stages of NK cell development to promote expression of critical transcriptional regulators including T-BET and ID2, NK cell receptors (NKRs) including NKp46, Ly49H, and Ly49D, and signaling molecules essential for NKR function. As a consequence, Ets1(-/-) NK cells fail to degranulate after stimulation through activating NKRs. Nonetheless, these cells are hyperresponsive to cytokines and have characteristics of chronic stimulation including increased expression of inhibitory NKRs and multiple activation-associated genes. Therefore, ETS1 regulates a broad gene expression program in NK cells that promotes target cell recognition while limiting cytokine-driven activation.
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