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

Publié dans: Immunity, 2016, 44 (1), pp.103-115. ⟨10.1016/j.immuni.2015.12.007⟩

Auteurs: 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, Nicholas D. Huntington

Résumé

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.

Lien vers HAL – hal-01440246

Lien vers le DOI – 10.1016/j.immuni.2015.12.007