Abstract
Abstract Natural killer (NK) cells are innate lymphocytes capable of killing virally infected cells or transformed cells. NK cells differentiate in the bone marrow before they migrate out to peripheral organs. The developmental program leading to functionally mature NK cells has been studied in the context of several transcription factors. However, the role of GATA-3 in NK cell development has not been completely understood. Using NK-cell specific Gata3 knockout mice (NK-Gata3-/-), we demonstrated that GATA-3 is required for the NK cell maturation beyond the CD27 single positive stage and for efficient IFN-g production. The frequencies of NK cells from NK-Gata3-/- mice were found higher in the bone marrow but lower in peripheral organs compared to control littermates, indicating that GATA-3 controls the maturation program required for bone marrow egress. Despite this, upon MCMV infection, NK cells from NK-Gata3-/- mice were able to expand vigorously, achieving NK cell frequencies surpassing those in controls, and therefore provided comparable protection. The enhanced proliferation of GATA-3-deficient NK cells was associated with enhanced upregulation of CD25 expression. Thus, the NK-Gata3-/- mice serve as a model to study the NK cell developmental process linked to cell migration, effector functions and proliferation.
Published Version
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