Identification of aceNKPs, a committed common progenitor population of the ILC1 and NK cell continuum

The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC hematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution, we have characterized bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC I/NK cell progenitors (ILC I/NKP), which we call "aceNKPs", are defined as lineage Id2(+) IL-7R alpha' CD25 (x4P7 NKG2A/C/E'Bc11 lb. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for ft-15, and produce IFN-gamma and perform upon IL-15 stimulation. Following reconstitution of Rag2(-/-)II2rg(-/-) hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells (regardless of their tissue location) that cannot be clearly segregated into the traditional ILC1 and NK subsets, suggesting that group 1 ILCs constitute a dynamic continuum of ILCs that can develop from a common progenitor. In addition, aceNKP-derived 1LCl/NK cells effectively ameliorate tumor burden in a model of lung metastasis, where they acquired a cytotoxic NK cell phenotype. Our results identify the primary ILCI/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing.