Content area
Abstract
Natural killer (NK) cells are a type of innate lymphoid cell specialized in providing defense against viruses and cells that have undergone transformation. The effector functions of NK cells are primarily mediated through the release of granzyme- and perforin-containing cytoplasmic granules that trigger target cell death. Cytolytic capacity of NK cells increases with functional maturation that is controlled by an incompletely defined network of transcription factors and cytokines. Here we show that mice with conditional deletion of the transcription factor Foxp1 in the NK cell lineage have decreased proportions and total numbers of NK cells in the spleen and bone marrow. The NK cells that develop in the absence of Foxp1 exhibit significant impairment in their maturation profile and cytolytic functions when compared to Foxp1 sufficient NK cells. Yet, induction of interferon gamma (IFN-g) production in response to IL-12 and IL-18 was similar in Foxp1-sufficient and –deficient NK cells. These data provide the first evidence of a role for Foxp1 in NK cell biology and highlight a novel target for strategies aimed at enhancing or engineering NK cells in patients with tumors or infections.
