TY - BOOK AU - Rodriguez-Rodriguez,Noe AU - Clark,Paula A. AU - Gogoi,Mayuri AU - Ferreira,Ana C.F. AU - Kerscher,Bernhard AU - Crisp,Alastair AU - Jolin,Helen E. AU - Murphy,Jane E. AU - Sivasubramaniam,Meera AU - Pedro,Luisa AU - Walker,Jennifer A. AU - Heycock,Morgan W.D. AU - Shields,Jacqueline D. AU - Barlow,Jillian L. AU - McKenzie,Andrew N.J. TI - Identification of aceNKPs, a committed common progenitor population of the ILC1 and NK cell continuum PY - 2022///-11-29 PB - National Academy of Sciences, KW - Text KW - local N1 - /pmc/articles/PMC7614094; /pubmed/36442116 N2 - 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 ILC1/NK cell progenitors (ILC1/NKP), which we call "aceNKPs", are defined as lineage(-)Id2(+)IL-7Rα(+)CD25(-)α4β7(-)NKG2A/C/E(+)Bcl11b(-). In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-γ and perforin upon IL-15 stimulation. Following reconstitution of Rag2(-/-)Il2rg(-/-) 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 ILC1/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 ILC1/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing UR - http://dx.doi.org/10.1073/pnas.2203454119 ER -