PLZF expression maps the early stages of ILC1 lineage development (LYM2P.720)

Among the variety of tissue-resident NK-like populations recently distinguished from classical recirculating cNK cells, liver innate lymphoid cells type I (ILC1) have been shown to represent a distinct lineage that originates from a novel PLZF-expressing ILC precursor (ILCP) strictly committed to the ILC1, ILC2 and ILC3 lineages. Here, using PLZF-reporter mice and cell transfer assays, we studied the developmental progression of ILC1s and demonstrated substantial overlap with stages previously ascribed to the cNK lineage, including pre-pro-NK, pre-NK precursor (pre-NKP), refined NKP (rNKP) and immature NK (iNK). Although they originated from different precursors, the ILC1 and cNK lineages followed a parallel progression at early stages and diverged later at the iNK stage, with a striking predominance of ILC1s over cNKs early in ontogeny. While a limited set of ILC1 genes were dependent on PLZF for expression, characteristically including Il7r , most of these genes were also differentially expressed between ILC1s and cNKs, indicating that PLZF together with other, yet to be defined, factors contribute to the divergence between these lineages.