Newly identified role for the transcription factor Foxp1 in natural killer cells

Abstract

Abstract Natural killer (NK) cells are innate lymphocytes critical for defense against pathogenic microbes and tumors. To understand dysfunction of NK cells in disease and to facilitate effective use of NK cells as therapeutic agents in the clinic, there is a critical need to ascertain the molecular mechanisms that regulate acquisition of optimum functionality of these cells. The functional maturation of NK cells is controlled by an incompletely defined network of transcription factors, which was recently expanded to implicate numerous factors, including Foxp1, that have never been studied in these cells. We show that mice with conditional deletion of the transcription factor Foxp1 in the NK cell lineage have substantially reduced frequencies of NK cells. The remaining NK cells in these mice exhibit an immature phenotype with reduced capacity to kill tumor target cells. The identification of a role of Foxp1 in development of highly functional NK cells is significant for the development of new strategies to promote or engineer highly functional NK cells to treat patients with tumors or infections. Supported by R01 AI148080