Transcriptome analysis reveals similarities between human blood CD3 CD56 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 CD16 and CD3 CD56 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 cells, by gene set enrichment analysis. Conversely, the signature genes of mouse NK cells are enriched in human CD56 cells. Correlations are based upon large differences in expression of a few key genes. CD56 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 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 cells, while IKZF3 (AIOLOS), TBX21 (T-bet), NFIL3 (E4BP4), ZEB2, PRDM1 (BLIMP1), and RORA mRNA levels are higher in CD56 cells.