@article{b7fcb1d57dbc4003a15b13236b46ef7b,
title = "Stage-Specific Requirement for Eomes in Mature NK Cell Homeostasis and Cytotoxicity",
abstract = "Natural killer (NK) cells are cytotoxic innate lymphoid cells (ILCs) that mediate antiviral and antitumor responses and require the transcriptional regulator Eomesodermin (Eomes) for early development. However, the role of Eomes and its molecular program in mature NK cell biology is unclear. To address this, we develop a tamoxifen-inducible, type-1-ILC-specific (Ncr1-targeted) cre mouse and combine this with Eomes-floxed mice. Eomes deletion after normal NK cell ontogeny results in a rapid loss of NK cells (but not ILC1s), with a particularly profound effect on penultimately mature stage III NK cells. Mechanisms responsible for stage III reduction include increased apoptosis and impaired maturation from stage II precursors. Induced Eomes deletion also decreases NK cell cytotoxicity and abrogates in vivo rejection of major histocompatibility complex (MHC)-class-I-deficient cells. However, other NK cell functional responses, and stage IV NK cells, are largely preserved. These data indicate that mature NK cells have distinct Eomes-dependent and -independent stages.",
keywords = "Eomes, NK cell, Ncr1-specific, cytotoxicity, homeostasis, in vivo, inducible-cre model, innate lymphoid cell, maturation",
author = "Wagner, {Julia A.} and Pamela Wong and Timothy Schappe and Berrien-Elliott, {Melissa M.} and Celia Cubitt and Natalia Jaeger and Madeline Lee and Keppel, {Cassie R.} and Marin, {Nancy D.} and Foltz, {Jennifer A.} and Lynne Marsala and Neal, {Carly C.} and Sullivan, {Ryan P.} and Schneider, {Stephanie E.} and Keppel, {Molly P.} and Nermina Saucier and Cooper, {Megan A.} and Fehniger, {Todd A.}",
note = "Funding Information: This work was supported by grants from the Howard Hughes Medical Institute (Medical Fellow Award to J.A.W.), the NIH (T32 HL007088 to J.A.W. P.W. and J.A.F.), and the NIH/NCI (F32 CA200253 to M.M.B.-E.; K12 5K12CA167540 to M.M.B.-E.; R01AI127752 to M.A.C.; and R01 AI102924, R01 CA205239, and P50 CA171963 to T.A.F.). We acknowledge the use of the Siteman Flow Core and Genome Technology Access center (NIH grant P30 CA91842) for this study. We thank Drs. Wayne Yokoyama, Daniel Link, Timothy Ley, and Anthony R. French for insightful discussion. J.A.W. P.W. and T.A.F. conceived and designed the study. All authors collected, analyzed, or assembled the data. J.A.W. P.W. and T.A.F. wrote the manuscript. All authors reviewed the data and edited and approved the final version of the manuscript. The authors declare no competing interests. Funding Information: This work was supported by grants from the Howard Hughes Medical Institute (Medical Fellow Award to J.A.W.), the NIH ( T32 HL007088 to J.A.W., P.W., and J.A.F.), and the NIH/NCI ( F32 CA200253 to M.M.B.-E.; K12 5K12CA167540 to M.M.B.-E.; R01AI127752 to M.A.C.; and R01 AI102924 , R01 CA205239 , and P50 CA171963 to T.A.F.). We acknowledge the use of the Siteman Flow Core and Genome Technology Access center ( NIH grant P30 CA91842 ) for this study. We thank Drs. Wayne Yokoyama, Daniel Link, Timothy Ley, and Anthony R. French for insightful discussion. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = jun,
day = "2",
doi = "10.1016/j.celrep.2020.107720",
language = "English",
volume = "31",
journal = "Cell Reports",
issn = "2211-1247",
number = "9",
}