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Identification of lineage-specifying cytokines that signal all CD8+-cytotoxic-lineage-fate 'decisions' in the thymus.
Nature Immunology ( IF 30.5 ) Pub Date : 2017-Nov-01 , DOI: 10.1038/ni.3847
Ruth Etzensperger , Tejas Kadakia , Xuguang Tai , Amala Alag , Terry I Guinter , Takeshi Egawa , Batu Erman , Alfred Singer

T cell antigen receptor (TCR) signaling in the thymus initiates positive selection, but the CD8+-lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We have identified four cytokines (IL-6, IFN-γ, TSLP and TGF-β) that did not signal via the common γ-chain (γc) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying transcription factor Runx3d and signaled the generation of CD8+ T cells. Elimination of in vivo signaling by all six of these 'lineage-specifying cytokines' during positive selection eliminated Runx3d expression and completely abolished the generation of CD8+ single-positive thymocytes. Thus, this study proves that signaling during positive selection by lineage-specifying cytokines is responsible for all CD8+-lineage-fate 'decisions' in the thymus.

中文翻译:

鉴定能在胸腺中发出所有CD8 +-细胞毒性-谱系命运“决定”信号的谱系特异性细胞因子。

胸腺中的T细胞抗原受体(TCR)信号启动了积极的选择,但在TCR信号终止后,CD8 +谱系的命运被认为是由细胞因子诱导的,尽管这仍存在争议且未经证实。我们已经确定了四个细胞因子(IL-6,IFN-γ,TSLP和TGF-β),其不经公共γ链信号(γ Ç)受体,但是,如IL-7和IL-15诱导的表达谱系特异性转录因子Runx3d并指示CD8 + T细胞的生成。在阳性选择过程中,所有这六种“谱系特异性细胞因子”消除了体内信号传导,从而消除了Runx3d表达,并完全消除了CD8 +的产生单阳性胸腺细胞。因此,这项研究证明,通过谱系确定性细胞因子进行阳性选择期间的信号传导是胸腺中所有CD8 +谱系命运“决定”的原因。
更新日期:2017-09-28
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