The developmental relationship of ILCs. The NK cell progenitor (pre-NK) and the ILC progenitor (pre-ILC) evolve from the common lymphoid progenitor (CLP), but the phenotype and developmental requirements of the pre-ILCs have not been defined in humans (dotted lines). ILC3s and ILC2s develop from pre-ILCs under the influence of the transcription factors RORγt and GATA3, respectively. CD127⁺ ILC1s may derive from pre-ILCs or may be developmentally separated as part of the NK branch together with conventional NK cells (cNK) and CD127^low ILC1s. Inset: ILCs have plasticity, as RORγt⁺ NCR⁻ ILC3 can differentiate in vitro into ILC1s and into NCR⁺ ILC3s; the latter, in turn, can be induced into a NKp44⁻ cKit⁻ CRTH2⁻ ILC1s, and vice versa, depending on specific activation signals. Whether these ILC1s are similar to the NKp44⁻ cKit⁻ CRTH2⁻ ILC1s that can be found in human tissues and blood remains to be determined. During these processes, these cells downregulate RORγt and upregulate Tbet.