Figure 1.

Innate lymphoid cell lineage and classification. Innate lymphoid cells (ILCs) derive from common lymphoid progenitors (CLPs) and give rise to common innate lymphoid progenitors (CILPs) and common helper innate lymphoid progenitors (CHILPs). CILPs differentiate into natural killer (NK) cell progenitors (NKPs) and then terminally differentiate into NK cells. CHILPs divide into innate lymphoid cell progenitors (ILCPs) and lymphoid tissue inducer progenitors (LTiPs), which generate all helper-like ILC subsets, ILC1s, ILC2s, ILC3s, and LTis, respectively. The transcriptional repressor Id2 is developmentally required and sequentially expressed in the ILC precursors. Id2-dependent precursors can further differentiate with lineage-specific transcription factors. Recent studies suggest that Zbtb16⁺ILCPs harbored extensive NK and/or ILC precursors potential, indicating a revised model for ILC differentiation. The different ILC subsets need their unique transcription factors for development and secretion of their signature cytokines in response to different stimulators, which mirror the phenotype and the function of adaptive helper T cells, Th1, Th2, and Th17, respectively.