The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15

Rebecca B. Delconte; Wei Shi; Priyanka Sathe; Takashi Ushiki; Cyril Seillet; Martina Minnich; Tatiana B Kolesnik; Lucille C. Rankin; Lisa A Mielke; Jian-Guo Zhang; Meinrad Busslinger; Mark J. Smyth; Dana S. Hutchinson; Stephen L Nutt; Sandra E Nicholson; Warren S. Alexander; Lynn M. Corcoran; Eric Vivier; Gabrielle T Belz; Sebastian Carotta; Nicholas D Huntington

doi:10.1016/j.immuni.2015.12.007

The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15

Rebecca B. Delconte, Wei Shi, Priyanka Sathe, Takashi Ushiki, Cyril Seillet, Martina Minnich, Tatiana B Kolesnik, Lucille C. Rankin, Lisa A Mielke, Jian-Guo Zhang, Meinrad Busslinger, Mark J. Smyth, Dana S. Hutchinson, Stephen L Nutt, Sandra E Nicholson, Warren S. Alexander, Lynn M. Corcoran, Eric Vivier, Gabrielle T Belz, Sebastian CarottaNicholas D Huntington

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

The inhibitor of DNA binding 2 (Id2) is essential for natural killer (NK) cell development with its canonical role being to antagonize E-protein function and alternate lineage fate. Here we have identified a key role for Id2 in regulating interleukin-15 (IL-15) receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Id2 deletion in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling and metabolic function and this could be rescued by strong IL-15 receptor stimulation or genetic ablation of Socs3. During NK cell maturation, we observed an inverse correlation between E-protein target genes and Id2. These results shift the current paradigm on the role of ID2, indicating that it is required not only to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Id2 is essential for natural killer cell development. Huntington and colleagues demonstrate that Id2 acts as a rheostat to control IL-15 receptor signaling and natural killer cell fate.

Original language	English
Pages (from-to)	103-115
Number of pages	13
Journal	Immunity
Volume	44
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2015.12.007
Publication status	Published - 19 Jan 2016

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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., Busslinger, M., Smyth, M. J., Hutchinson, D. S., Nutt, S. L., Nicholson, S. E., Alexander, W. S., Corcoran, L. M., Vivier, E., Belz, G. T., ... Huntington, N. D. (2016). The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15. Immunity, 44(1), 103-115. https://doi.org/10.1016/j.immuni.2015.12.007

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title = "The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15",

abstract = "The inhibitor of DNA binding 2 (Id2) is essential for natural killer (NK) cell development with its canonical role being to antagonize E-protein function and alternate lineage fate. Here we have identified a key role for Id2 in regulating interleukin-15 (IL-15) receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Id2 deletion in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling and metabolic function and this could be rescued by strong IL-15 receptor stimulation or genetic ablation of Socs3. During NK cell maturation, we observed an inverse correlation between E-protein target genes and Id2. These results shift the current paradigm on the role of ID2, indicating that it is required not only to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Id2 is essential for natural killer cell development. Huntington and colleagues demonstrate that Id2 acts as a rheostat to control IL-15 receptor signaling and natural killer cell fate.",

author = "Delconte, {Rebecca B.} and Wei Shi and Priyanka Sathe and Takashi Ushiki and Cyril Seillet and Martina Minnich and Kolesnik, {Tatiana B} and Rankin, {Lucille C.} and Mielke, {Lisa A} and Jian-Guo Zhang and Meinrad Busslinger and Smyth, {Mark J.} and Hutchinson, {Dana S.} and Nutt, {Stephen L} and Nicholson, {Sandra E} and Alexander, {Warren S.} and Corcoran, {Lynn M.} and Eric Vivier and Belz, {Gabrielle T} and Sebastian Carotta and Huntington, {Nicholas D}",

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Delconte, RB, Shi, W, Sathe, P, Ushiki, T, Seillet, C, Minnich, M, Kolesnik, TB, Rankin, LC, Mielke, LA, Zhang, J-G, Busslinger, M, Smyth, MJ, Hutchinson, DS, Nutt, SL, Nicholson, SE, Alexander, WS, Corcoran, LM, Vivier, E, Belz, GT, Carotta, S & Huntington, ND 2016, 'The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15', Immunity, vol. 44, no. 1, pp. 103-115. https://doi.org/10.1016/j.immuni.2015.12.007

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AU - Delconte, Rebecca B.

AU - Shi, Wei

AU - Sathe, Priyanka

AU - Ushiki, Takashi

AU - Seillet, Cyril

AU - Minnich, Martina

AU - Kolesnik, Tatiana B

AU - Rankin, Lucille C.

AU - Mielke, Lisa A

AU - Zhang, Jian-Guo

AU - Busslinger, Meinrad

AU - Smyth, Mark J.

AU - Hutchinson, Dana S.

AU - Nutt, Stephen L

AU - Nicholson, Sandra E

AU - Alexander, Warren S.

AU - Corcoran, Lynn M.

AU - Vivier, Eric

AU - Belz, Gabrielle T

AU - Carotta, Sebastian

AU - Huntington, Nicholas D

PY - 2016/1/19

Y1 - 2016/1/19

N2 - The inhibitor of DNA binding 2 (Id2) is essential for natural killer (NK) cell development with its canonical role being to antagonize E-protein function and alternate lineage fate. Here we have identified a key role for Id2 in regulating interleukin-15 (IL-15) receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Id2 deletion in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling and metabolic function and this could be rescued by strong IL-15 receptor stimulation or genetic ablation of Socs3. During NK cell maturation, we observed an inverse correlation between E-protein target genes and Id2. These results shift the current paradigm on the role of ID2, indicating that it is required not only to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Id2 is essential for natural killer cell development. Huntington and colleagues demonstrate that Id2 acts as a rheostat to control IL-15 receptor signaling and natural killer cell fate.

AB - The inhibitor of DNA binding 2 (Id2) is essential for natural killer (NK) cell development with its canonical role being to antagonize E-protein function and alternate lineage fate. Here we have identified a key role for Id2 in regulating interleukin-15 (IL-15) receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Id2 deletion in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling and metabolic function and this could be rescued by strong IL-15 receptor stimulation or genetic ablation of Socs3. During NK cell maturation, we observed an inverse correlation between E-protein target genes and Id2. These results shift the current paradigm on the role of ID2, indicating that it is required not only to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Id2 is essential for natural killer cell development. Huntington and colleagues demonstrate that Id2 acts as a rheostat to control IL-15 receptor signaling and natural killer cell fate.

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DO - 10.1016/j.immuni.2015.12.007

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AN - SCOPUS:84958841305

VL - 44

SP - 103

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JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 1

ER -

The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15

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Alteration of glucose metabolism by GPCR activation

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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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Alteration of glucose metabolism by GPCR activation

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