The innate lymphoid cell (ILC) group, composed of helper (ILC1, ILC2 and ILC3) and cytotoxic subsets (NK cells), arises from ILC-committed precursors (ILCPs). In Cell, Di Santo and colleagues identify CD117+ ILCPs at low frequency in human peripheral blood (PB). This population lacks expression of signature transcription factor genes associated with the various ILC subsets; instead these genes are in an epigenetically poised state. In vitro stimulation with defined cytokine cocktails or clonal analysis after culture on OP9 cells shows that the PB ILCPs have the potential to give rise to any of the ILC subsets in a uni- and/or multipotent manner but have no T or B cell potential. Similarly, immune-deficient mice 'humanized' with CD117+ PB ILCPs generate ILC populations that include NK cells in various tissues—lymphoid and non-lymphoid. Humans therefore possess a circulating ILC precursor population that can seed peripheral tissues and, with the appropriate environmental cues, give rise to all ILC populations.

Cell (9 March 2017) doi:10.1016/j.cell.2017.02.021