The Helix-Loop-Helix protein ID2 governs NK cell fate by tuning their sensitivity to Interleukin-15
Publication Year 2016-01-19, Volume 44, Issue #1, Page 103-15
Journal Title
Publication Type
Journal Article
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.
Cell Press
WEHI Research Division(s)
Molecular Immunology; Bioinformatics; Population Health And Immunity; Cancer And Haematology; Inflammation
PubMed ID
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Creation Date: 2016-01-29 11:46:01
Last Modified: 2018-01-09 12:55:40
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