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Identification that Nfil3 is critical for NK cell but not ILC1 development in the liver of mice.
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The helix–loop–helix protein ID2 governs NK cell fate by tuning their sensitivity to interleukin-15
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These data identify the mechanistic requirement for ID2 in NK cell homeostasis. ID2 is constantly required to suppress E2A-target genes and maintain optimal IL-15 signaling.
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9•• Delconte, R.B., Shi, W., Sathe, P., Ushiki, T., Seillet, C., Minnich, M., Kolesnik, T.B., Rankin, L.C., Mielke, L.A., Zhang, J.G., et al. The helix–loop–helix protein ID2 governs NK cell fate by tuning their sensitivity to interleukin-15. Immunity 44 (2016), 103–115 These data identify the mechanistic requirement for ID2 in NK cell homeostasis. ID2 is constantly required to suppress E2A-target genes and maintain optimal IL-15 signaling.
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The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development
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14 Kallies, A., Carotta, S., Huntington, N.D., Bernard, N.J., Tarlinton, D.M., Smyth, M.J., Nutt, S.L., A role for Blimp1 in the transcriptional network controlling natural killer cell maturation. Blood 117 (2011), 1869–1879.
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Peripheral natural killer cell maturation depends on the transcription factor Aiolos
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These two papers identify transcription factors critical for the differentiation and effector function of NK cells. Ikzf3 is required for the terminal NK cell differentiation whereas Zeb2, like Tbx21 is required for entry into the mature NK cell pool.
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15• Holmes, M.L., Huntington, N.D., Thong, R.P., Brady, J., Hayakawa, Y., Andoniou, C.E., Fleming, P., Shi, W., Smyth, G.K., Degli-Esposti, M.A., et al. Peripheral natural killer cell maturation depends on the transcription factor Aiolos. EMBO J 33 (2014), 2721–2734 These two papers identify transcription factors critical for the differentiation and effector function of NK cells. Ikzf3 is required for the terminal NK cell differentiation whereas Zeb2, like Tbx21 is required for entry into the mature NK cell pool.
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Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis
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17 Burkett, P.R., Koka, R., Chien, M., Chai, S., Boone, D.L., Ma, A., Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis. J Exp Med 200 (2004), 825–834.
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Circulating IL-15 exists as heterodimeric complex with soluble IL-15Ralpha in human and mouse serum
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20 Bergamaschi, C., Bear, J., Rosati, M., Beach, R.K., Alicea, C., Sowder, R., Chertova, E., Rosenberg, S.A., Felber, B.K., Pavlakis, G.N., Circulating IL-15 exists as heterodimeric complex with soluble IL-15Ralpha in human and mouse serum. Blood 120 (2012), e1–e8.
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23 Cooper, M.A., Bush, J.E., Fehniger, T.A., VanDeusen, J.B., Waite, R.E., Liu, Y., Aguila, H.L., Caligiuri, M.A., In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100 (2002), 3633–3638.
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24 Koka, R., Burkett, P.R., Chien, M., Chai, S., Chan, F., Lodolce, J.P., Boone, D.L., Ma, A., Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice. J Exp Med 197 (2003), 977–984.
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25 Sandau, M.M., Schluns, K.S., Lefrancois, L., Jameson, S.C., Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells. J Immunol 173 (2004), 6537–6541.
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26 Kennedy, M.K., Glaccum, M., Brown, S.N., Butz, E.A., Viney, J.L., Embers, M., Matsuki, N., Charrier, K., Sedger, L., Willis, C.R., et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191 (2000), 771–780.
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27 Castillo, E.F., Acero, L.F., Stonier, S.W., Zhou, D., Schluns, K.S., Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation. Blood 116 (2010), 2494–2503.
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31 Colpitts, S.L., Stoklasek, T.A., Plumlee, C.R., Obar, J.J., Guo, C., Lefrancois, L., Cutting edge: the role of IFN-alpha receptor and MyD88 signaling in induction of IL-15 expression in vivo. J Immunol 188 (2012), 2483–2487.
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Conclusive evidence that the STAT5-target gene Mcl1, is essential for NK cell survival. This finding allowed the authors to generate a specific NK cell null mouse for cancer studies.
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36• Sathe, P., Delconte, R.B., Souza-Fonseca-Guimaraes, F., Seillet, C., Chopin, M., Vandenberg, C.J., Rankin, L.C., Mielke, L.A., Vikstrom, I., Kolesnik, T.B., et al. Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. Nat Commun, 5, 2014, 4539 Conclusive evidence that the STAT5-target gene Mcl1, is essential for NK cell survival. This finding allowed the authors to generate a specific NK cell null mouse for cancer studies.
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37
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The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells
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Elegant and detailed study into the role of the mTOR pathway in NK cell metabolism in mice. mTOR signaling was essential for NK cell development and differentiation in vivo and its activity was governed by IL-15.
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37•• Marcais, A., Cherfils-Vicini, J., Viant, C., Degouve, S., Viel, S., Fenis, A., Rabilloud, J., Mayol, K., Tavares, A., Bienvenu, J., et al. The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells. Nat Immunol 15 (2014), 749–757 Elegant and detailed study into the role of the mTOR pathway in NK cell metabolism in mice. mTOR signaling was essential for NK cell development and differentiation in vivo and its activity was governed by IL-15.
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38
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