The impact of stress on the transcriptomic signature of iNKT1 cells

Invariant natural killer T (iNKT) cells develop in thymus before emigrating and settling peripheral tissues and organs. In contrast to regular naive T cells, most iNKT cells do not continuously recirculate but are rather sessile and can adopt phenotypically as well as functionally to their tissue environment. To explore this in more detail, we focused on the most widely distributed CD4(+)iNKT1 cells and compared the transcriptome of cells isolated from liver and spleen. Whereas there are only very few genuine differences in the transcriptomes of CD4(+)iNKT1 cells of these two organs, the mode of cell isolation left clear marks in the transcriptomic signature. In contrast to liver cell isolated in the cold, cells prepared by enzymatic tissue digestion upregulated quickly a series of genes known to respond to stress. Therefore, to avoid erroneous conclusions, a comparison of expression profiles must take into consideration the history of cell preparation.

Automated summary

Invariant natural killer T (iNKT) cells develop in the thymus and then migrate to peripheral tissues and organs, adapting phenotypically and functionally to the tissue environment. A study comparing CD4(+) iNKT1 cells isolated from the liver and spleen found minimal genuine transcriptomic differences, with the method of cell isolation affecting the transcriptomic signature. Cells isolated via enzymatic digestion of tissue showed upregulation of stress response genes compared to cells isolated in cold conditions, emphasizing the importance of considering cell preparation history in expression profile comparisons.