The Transcriptional Repressor Gfi1 Plays a Critical Role in the Development of NKT1- and NKT2-Type iNKT Cells

Abstract

<div><p>Gfi1 plays an important role in the development and maintenance of many hematopoietic linage cells. However, the impact of <i>Gfi1</i>-deficiency on the iNKT cell differentiation remains unclear. We herein demonstrate a critical role of Gfi1 in regulating the development of iNKT cell subsets. In the thymus of T cell-specific <i>Gfi1</i>-deficient mice, iNKT cells normally developed up to stage 2, while the number of stage 3 NK1.1^pos iNKT cells was significantly reduced. Furthermore, CD4^pos iNKT cells were selectively reduced in the peripheral organs of T cell-specific <i>Gfi1</i>-deficient mice. The α-GalCer-dependent production of IFN-γand Th2 cytokines, but not IL-17A, was severely reduced in T cell-specific <i>Gfi1</i>-deficient mice. In addition, a reduction of the α-GalCer-induced anti-tumor activity was observed in <i>Gfi1</i>-deficient mice. These findings demonstrate the important role of Gfi1 in regulating the development and function of NKT1- and NKT2-type iNKT cell subsets.</p></div