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, Carotta, Sebastian and Huntington, Nicholas D. (2016) The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15. Immunity, 44 1: 103-115. doi:10.1016/j.immuni.2015.12.007

Author 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
Carotta, Sebastian
Huntington, Nicholas D.
Title The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15
Journal name Immunity   Check publisher's open access policy
ISSN 1097-4180
Publication date 2016-01-19
Sub-type Article (original research)
DOI 10.1016/j.immuni.2015.12.007
Open Access Status Not Open Access
Volume 44
Issue 1
Start page 103
End page 115
Total pages 14
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Subject 2723 Immunology and Allergy
2403 Immunology
2725 Infectious Diseases
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Sub-type: Article (original research)
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