TY - JOUR
T1 - Identification of aceNKPs, a committed common progenitor population of the ILC1 and NK cell continuum
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.
PY - 2022/12/6
Y1 - 2022/12/6
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.
AB - 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.
KW - hematopoiesis
KW - ILC1s
KW - innate lymphoid cells
KW - NK cells
KW - NKG2A/C/E
U2 - 10.1073/pnas.2203454119
DO - 10.1073/pnas.2203454119
M3 - Article
C2 - 36442116
AN - SCOPUS:85142900869
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 49
M1 - e2203454119
ER -