Differentiation of c-Kit+ CD24+ natural killer cells into myeloid cells in a GATA-2-dependent manner

Myeloid progenitor cells have generally been considered the predominant source of myeloid cells under steady-state conditions. Here we show that NK cells contributed to a myeloid cell lineage pool in naïve and tumor-bearing mice. Using fate tracing of NKp46⁺ cells, we found that myeloid cells could be derived from NK cells. Notably, among mature CD11b⁺ CD27⁺ NK cells, c-Kit⁺ CD24⁺ NK cells were capable of differentiating into a range of myeloid lineages in vitro and produced neutrophils and monocytes in vivo. The differentiation was completely inhibited by NK-stimulating cytokines. In addition to the potential for differentiation into myeloid cells, c-Kit⁺ CD24⁺ NK cells retained NK cell phenotypes and effector functions. Mechanistically, GATA-2 was necessary for the differentiation of c-Kit⁺ CD24⁺ NK cells. Therefore, we discovered that GATA-2-dependent differentiation of c-Kit⁺ CD24⁺ NK cells contributes to myeloid cell development and identified a novel pathway for myeloid lineage commitment under physiological conditions.