Stage Specific Role for Ets1 Transcription Factor in Natural Killer Cell Maintenance

Natural killer (NK) cells are a group of innate immune cells known for their ability to lyse target cells without prior exposure and are among the first responders in any illness. E26 transformation specific sequence (Ets1) is a developmentally restricted transcription factor found in immune tissues where it is critical for the development of lymphoid cells. Our laboratory and others have previously determined that Ets1 is necessary for complete NK cell development and function by generating an Ets1 global knockout mouse model. However, the Ets1 global knockout mouse model neither assesses the cell extrinsic and intrinsic functions of Ets1 nor does it assess Ets1 dependency at different stages of NK maturation. To address these concerns, we have developed and herein present a novel NK cell specific NKp46iCre mediated conditional deletion of Ets1 in a genetically engineered floxed Ets1 mouse model, NKp46iCre-Ets1fl/fl. Using a comprehensive NK cell development panel for multi-color flow cytometry, a 70% reduction of total NK cells was demonstrated in bone marrow, spleen and blood in the NKp46iCre -Ets1fl/fl compared to the Ets1fl/fl and the NKp46iCre controls. We further observed a stage specific reduction in mature NK cells in the NKp46iCre -Ets1fl/fl compared to relevant controls suggesting that Ets1 may be necessary for NK maturation and maintenance in addition to early NK cell development. Our findings not only confirm the intrinsic role of Ets1 in early NK cell development but also introduce a new role for Ets1 in the maintenance of the NK lineage as they mature to cytotoxic NK cells.Undergraduate Research OfficePelotonia FellowshipNo embargoAcademic Major: Microbiolog