Unraveling Natural Killer T-Cells Development

Sabrina Bianca Bennstein, Sabrina Bianca Bennstein

Abstract

Natural killer T-cells are a subset of innate-like T-cells with the ability to bridge innate and adaptive immunity. There is great interest in harnessing these cells to improve tumor therapy; however, greater understanding of invariant NKT (iNKT) cell biology is needed. The first step is to learn more about NKT development within the thymus. Recent studies suggest lineage separation of murine iNKT cells into iNKT1, iNKT2, and iNKT17 cells instead of shared developmental stages. This review will focus on these new studies and will discuss the evidence for lineage separation in contrast to shared developmental stages. The author will also highlight the classifications of murine iNKT cells according to identified transcription factors and cytokine production, and will discuss transcriptional and posttranscriptional regulations, and the role of mammalian target of rapamycin. Finally, the importance of these findings for human cancer therapy will be briefly discussed.

Keywords: invariant NKT cells; natural killer T cells; natural killer T development; natural killer T lineage; natural killer T subsets; natural killer T type II cells.

Figures

Figure 1
Figure 1
Schematic fluorescence-activated cell scanning plot depicting the three identified invariant NKT (iNKT) subsets within the described developmental stages, according to NK1.1 and CD44 expression. Red dots are iNKT2 cells, green dots are iNKT17 cells, and blue dots are iNKT1 cells. The beige dot represents a stage 0 iNKT cell, which expresses the transcription factors Erg2 and PLZF, and decreases CD24 and CD69 expression during the development into stage 1 NKT cells (26, 28, 29).
Figure 2
Figure 2
iNKT1, iNKT2, and iNKT17 displayed with their transcription factors (TF), cell surface molecules, and cytokine secretion. Diagram legends: – inhibiting, ↑ upregulated, → expressed TF (–29, 34, 35, 41).

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