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

被引：101

作者：

Delconte, Rebecca B. ^{[1
,2
]}

Shi, Wei ^{[1
,2
,3
]}

Sathe, Priyanka ^{[1
,2
]}

Ushiki, Takashi ^{[1
,2
]}

Seillet, Cyril ^{[1
,2
]}

Minnich, Martina ^{[4
]}

Kolesnik, Tatiana B. ^{[1
,2
]}

Rankin, Lucille C. ^{[1
,2
]}

Mielke, Lisa A. ^{[1
,2
]}

Zhang, Jian-Guo ^{[1
,2
]}

Busslinger, Meinrad ^{[4
]}

Smyth, Mark J. ^{[5
,6
]}

Hutchinson, Dana S. ^{[7
]}

Nutt, Stephen L. ^{[1
,2
]}

Nicholson, Sandra E. ^{[1
,2
]}

Alexander, Warren S. ^{[1
,2
]}

Corcoran, Lynn M. ^{[1
,2
]}

Vivier, Eric ^{[8
,9
]}

Belz, Gabrielle T. ^{[1
,2
]}

Carotta, Sebastian ^{[1
,2
]}

Huntington, Nicholas D. ^{[1
,2
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia

[3] Univ Melbourne, Dept Comp & Informat Syst, Melbourne, Vic 3010, Australia

[4] Res Inst Mol Pathol, A-1030 Vienna, Austria

[5] QIMR Berghofer Med Res Inst, Herston, Qld 4006, Australia

[6] Univ Queensland, Sch Med, Herston, Qld 4006, Australia

[7] Monash Inst Pharmacol Sci, Drug Discovery Biol, Parkville, Vic 3052, Australia

[8] Aix Marseille Univ UM2, INSERM, U1104, Ctr Immunol Marseille Luminy,CNRS,UMR7280, F-13288 Marseille, France

[9] Hop Comception, AP HM, Immunol, F-13385 Marseille, France

来源：

IMMUNITY | 2016年 / 44卷 / 01期

基金：

欧洲研究理事会; 英国医学研究理事会; 澳大利亚研究理事会;

关键词：

NATURAL-KILLER-CELL; TRANSCRIPTIONAL REGULATOR ID2; INNATE LYMPHOID-CELLS; IMMUNOGLOBULIN ENHANCER; EXPRESSION; CYTOKINE; SURVIVAL; IL-15; NFIL3; MAINTENANCE;

D O I：

10.1016/j.immuni.2015.12.007

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：103 / 115

页数：13

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