Role of GATA2 in Human NK Cell Development

Natural killer (NK) cells are major innate lymphocytes. NK cells do not require prior antigen exposure to mediate antitumor cytotoxicity or proinflammatory cytokine production. Since they use only nonclonotypic receptors, they possess high clinical value in treatment against a broad spectrum of malignancies. Irrespective of this potential, however, the transcriptional regulation that governs human NK cell development remains far from fully defined. Various environmental cues initiate a complex network of transcription factors (TFs) during their early development, one of which is GATA2, a master regulator that drives the commitment of common lymphoid progenitors (CLPs) into immature NK progenitors (NKPs). GATA2 forms a core heptad complex with six other TFs (TAL1, FLI1, RUNX1, LYL1, LMO2, and ERG) to mediate its transcriptional regulation in various cell types. Patients with GATA2 haploinsufficiency specifically lose CD56bright NK cells, with or without a reduced number of CD56dlm NK cells. Here, we review the recent progress in understanding GATA2 and its role in human NK cell development and functions.