The Helix-Loop-Helix protein ID2 governs NK cell fate by tuning their sensitivity to Interleukin-15
- Author(s)
- Delconte, RB; Shi, W; Sathe, P; Ushiki, T; Seillet, C; Minnich, M; Kolesnik, TB; Rankin, LC; Mielke, LA; Zhang, JG; Busslinger, M; Smyth, MJ; Hutchinson, DS; Nutt, SL; Nicholson, SE; Alexander, WS; Corcoran, LM; Vivier, E; Belz, GT; Carotta, S; Huntington, ND;
- Details
- Publication Year 2016-01-19,Volume 44,Issue #1,Page 103-15
- Journal Title
- Immunity
- Publication Type
- Journal Article
- 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.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Immunology; Bioinformatics; Population Health And Immunity; Cancer And Haematology; Inflammation
- PubMed ID
- 26795246
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2015.12.007
- NHMRC Grants
- NHMRC/1027472, NHMRC/1047903, NHMRC/1016647, NHMRC/1049407, NHMRC/1066770, NHMRC/1057852,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-01-29 11:46:01
Last Modified: 2018-01-09 12:55:40