KLRG1 and NKp46 discriminate subpopulations of human CD117+ CRTH2- ILCs biased toward ILC2 or ILC3

Recently, circulating multi- and uni-potential human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lack CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets; the first expressed NKp46, the second expressed both NKp46 and CD56 and the third expressed KLRG1. Analysis of the differentiation potential of these cells on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically poised to differentiate to other ILC subsets depending on the activation signals they receive. 24 samples of 5 different cell types 6 replicates for 3 cell types and 3 replicates for 2 cell types