Transcriptome analysis reveals similarities between human blood CD3(−) CD56(bright) cells and mouse CD127(+) innate lymphoid cells

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.