Cutting edge: TCR-induced NAB2 enhances T cell function by coactivating IL-2 transcription

被引:35
作者
Collins, Samuel
Wolfraim, Lawrence A.
Drake, Charles G.
Horton, Maureen R.
Powell, Jonathan D.
机构
[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
[2] MaxCyte Inc, Gaithersburg, MD 20878 USA
[3] Johns Hopkins Univ, Sch Med, Div Pulm Med, Baltimore, MD 21231 USA
关键词
D O I
10.4049/jimmunol.177.12.8301
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
TCR engagement leads to the up-regulation of genetic programs that can both activate and inhibit T cell function. The early growth receptor (Egr)proteins Egr-2 and Egr-3 have recently been identified as TCR-induced negative regulators of T cell function. NAB2 (NGFI-A-binding protein 2) is both a coactivator and a corepressor of Egr-mediated transcription and has been implicated in regulating Schwann cell myelination. In this report we demonstrate that NAB2 is induced by TCR engagement and that its expression is enhanced by the presence of co-stimulation. The overexpression of NAB2 enhanced IL-2 production while small interfering RNA to NAB2 markedly inhibited IL-2 expression. Mechanistically, we demonstrate that NAB2 enhances IL-2 transcription by acting as a coactivator for Egr-1. Indeed, chromatin immuno-precipitation analysis reveals that NAB2 is recruited to the Egr-1 binding site of the IL-2 promoter. Taken together, our findings identify NAB2 as a novel coactivator of T cell-function.
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收藏
页码:8301 / 8305
页数:5
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