Transcription Factor TX Is Required for Liver-resident NK cells development

Abstract

Abstract Hepatic NK cells are heterogeneous populations, consisting of DX5+CD49a− NK cells and CD49a+DX5− NK cells. CD49a+DX5− NK cells, also termed “tissue-resident NK (trNK) cells”, are distinct from DX5+CD49a− conventional NK (cNK) cells and possess unique hallmarks. Recent study shows that trNK cell differentiation is programmed by transcription factor T-bet, instead of Eomes, which is critical for cNK cell development. T-bet is highly expressed by both trNK and cNK cells, its deficiency leads to dramatic reduction of trNK cell and terminal mature cNK cells, suggesting a non-specific role of T-bet in the development of NK cell subsets. To find a transcription factor that potentially impacts trNK cell development in a specific manner, we analyzed differentially expressed transcription factor genes between liver trNK and cNK cells by microarrays. We found that the transcription factor TX is expressed on liver trNK cells at much higher levels than on cNK cells. In order to figure out whether TX has an effect on liver trNK cells, we overexpressed TX on HSCs, and transferred the cells into lethally irradiated mice. Surprisingly, the frequency and number of liver trNK cells increased in TX-overexpressed mice. Then, we knocked down TX expression on HSCs, and transferred the cells to lethally irradiated mice. Although the frequency of liver trNK cells was invariant, the number decreased significantly. Therefore, these results suggest that the transcription factor TX affects liver trNK cells development, and the underlying mechanisms await further investigation.