Natural killer (NK) and Natural killer T (NKT) cells are important in host defense against pathogens, as well as for the initiation of adaptive immune responses. We and others have recently showed that miRNAs play important roles in NK and NKT cell development, maturation and function, but the roles of specific miRNAs are still lacking. Here we show that modulation of miR-150 expression levels has a differential effect on NK and NKT cell development. Mice with a targeted deletion of miR-150 have an impaired, stem cell-intrinsic defect in their ability to generate mature NK cells. Conversely, a gain-of-function miR-150 transgene promotes the development of NK cells, which display more mature phenotype and produce higher amounts of IFNγ following activation. In contrast, we find that overexpression of miR150 results in a substantial reduction of iNKT cells in the thymus and from the peripheral lymphoid organs. The transcription factor c-Myb has been shown to be a direct target of miR150, and we propose that miR-150 controls the development of NK and NKT cell lineages by targeting c-Myb. Our findings of the increased NK cell and decreased NKT cell frequencies in c-Myb heterozygous bone marrow chimeras are consistent with this hypothesis.
- Copyright © 2011 by The American Association of Immunologists, Inc.