Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2016-01, Vol.44 (1), p.103-115

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Id2 is upregulated during NK cell maturation to titrate E-protein activity•Id2 deletion in mature NK cells results in apoptosis•Id2 suppresses SOCS3 expression to maintain IL-15 receptor signaling•Requirement for Id2 is overcome by strong IL-15 receptor stimulation 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.