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Stage-Specific Requirement for Eomes in Mature NK Cell Homeostasis and Cytotoxicity.

Wagner, Julia A and Wong, Pamela and Schappe, Timothy and Berrien-Elliott, Melissa M and Cubitt, Celia and Jaeger, Natalia and Lee, Madeline and Keppel, Cassie R and Marin, Nancy D and Foltz, Jennifer A and Marsala, Lynne and Neal, Carly C and Sullivan, Ryan and Schneider, Stephanie E and Keppel, Molly P and Saucier, Nermina and Cooper, Megan A and Fehniger, Todd A (2020) Stage-Specific Requirement for Eomes in Mature NK Cell Homeostasis and Cytotoxicity. Cell reports, 31 (9). p. 107720. ISSN 2211-1247

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.

Item Type: Article
Date Deposited: 30 Jun 2020 00:45
Last Modified: 30 Jun 2020 00:45
URI: https://oak.novartis.com/id/eprint/42973

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