THEMIS: Two Models, Different Thresholds.

THEMIS: Two Models, Different Thresholds.
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主题:两个模型,不同的阈值。

DOI:
10.1016/j.it.2017.06.006
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发表时间:
2017-09
影响因子:
16.8
通讯作者:
Love PE
Love PE
中科院分区:
医学1区
文献类型:
--
作者:
Choi S;Cornall R;Lesourne R;Love PE

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THEMIS是最近发现的一种T细胞系限制性蛋白,是后生动物蛋白家族的创始成员。基因失活研究揭示了胸腺细胞阳性选择过程中对THEMIS的关键需求,暗示THEMIS参与T细胞抗原受体(TCR)下游的信号传导;但THEMIS功能的机制基础仍然难以捉摸。先前的模型假设THEMIS通过抑制TCR信号传导来防止胸腺细胞不适当地越过阳性/阴性选择阈值。然而,新的数据提出了一种替代模型,其中THEMIS增强TCR信号传导,使胸腺细胞能够达到阳性选择的阈值,避免因忽视而死亡。我们回顾了支持每个模型的数据,并得出结论,优势的证据有利于THEMIS在TCR信号传导中的增强功能。
THEMIS, a recently identified T-lineage restricted protein, is the founding member of a large metazoan protein family. Gene inactivation studies have revealed a critical requirement for THEMIS during thymocyte positive selection, implicating THEMIS in signaling downstream of the T cell antigen receptor (TCR); but the mechanistic underpinnings of THEMIS’ function have remained elusive. A previous model posited that THEMIS prevents thymocytes from inappropriately crossing the positive/negative selection threshold by dampening TCR signaling. However, new data suggest an alternative model where THEMIS enhances TCR signaling, enabling thymocytes to reach the threshold for positive selection avoiding death by neglect. We review the data supporting each model and conclude that the preponderance of evidence favors an enhancing function for THEMIS in TCR signaling.
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