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 & 1 others Nicholas D Huntington

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)

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 languageEnglish
Pages (from-to)103-115
Number of pages13
JournalImmunity
Volume44
Issue number1
DOIs
Publication statusPublished - 19 Jan 2016

Cite this

Delconte, Rebecca B. ; Shi, Wei ; Sathe, Priyanka ; Ushiki, Takashi ; Seillet, Cyril ; Minnich, Martina ; Kolesnik, Tatiana B ; Rankin, Lucille C. ; Mielke, Lisa A ; Zhang, Jian-Guo ; Busslinger, Meinrad ; Smyth, Mark J. ; Hutchinson, Dana S. ; Nutt, Stephen L ; Nicholson, Sandra E ; Alexander, Warren S. ; Corcoran, Lynn M. ; Vivier, Eric ; Belz, Gabrielle T ; Carotta, Sebastian ; Huntington, Nicholas D. / The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15. In: Immunity. 2016 ; Vol. 44, No. 1. pp. 103-115.
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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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doi = "10.1016/j.immuni.2015.12.007",
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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

The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15. / Delconte, Rebecca B.; Shi, Wei; Sathe, Priyanka; Ushiki, Takashi; Seillet, Cyril; Minnich, Martina; Kolesnik, Tatiana B; Rankin, Lucille C.; Mielke, Lisa A; Zhang, Jian-Guo; Busslinger, Meinrad; Smyth, Mark J.; Hutchinson, Dana S.; Nutt, Stephen L; Nicholson, Sandra E; Alexander, Warren S.; Corcoran, Lynn M.; Vivier, Eric; Belz, Gabrielle T; Carotta, Sebastian; Huntington, Nicholas D.

In: Immunity, Vol. 44, No. 1, 19.01.2016, p. 103-115.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15

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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U2 - 10.1016/j.immuni.2015.12.007

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