Transcriptome analysis reveals similarities between human blood CD3^- CD56^bright cells and mouse CD127⁺ innate...

For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3^- CD56^bright CD16^- and CD3^- CD56^dim CD16⁺ subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56^bright cells, by gene set enrichment analysis. Conversely, the signature genes of mouse NK cells are enriched in human CD56^dim cells. Correlations are based upon large differences in expression of a few key genes. CD56^bright cells show preferential expression of ILC-associated IL7R (CD127), TNFSF10 (TRAIL), KIT (CD117), IL2RA (CD25), CD27, CXCR3, DPP4 (CD26), GPR183, and MHC class II transcripts and proteins. This could indicate an ontological relationship between human CD56^bright cells and mouse CD127⁺ ILC, or conserved networks of transcriptional regulation. In line with the latter hypothesis, among transcription factors known to impact ILC or NK cell development, GATA3, TCF7 (TCF-1), AHR, SOX4, RUNX2, and ZEB1 transcript levels are higher in CD56^bright cells, while IKZF3 (AIOLOS), TBX21 (T-bet), NFIL3 (E4BP4), ZEB2, PRDM1 (BLIMP1), and RORA mRNA levels are higher in CD56^dim cells.