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An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function
Immunity ( IF 25.5 ) Pub Date : 2017-09-07 , DOI: 10.1016/j.immuni.2017.08.010
Hyunju Oh , Yenkel Grinberg-Bleyer , Will Liao , Dillon Maloney , Pingzhang Wang , Zikai Wu , Jiguang Wang , Dev M. Bhatt , Nicole Heise , Roland M. Schmid , Matthew S. Hayden , Ulf Klein , Raul Rabadan , Sankar Ghosh

Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles. c-Rel was critical for thymic Treg development while p65 was essential for mature Treg identity and maintenance of immune tolerance. Transcriptome and NF-κB p65 binding analyses demonstrated a lineage specific, NF-κB-dependent transcriptional program, enabled by enhanced chromatin accessibility. These dual roles of canonical NF-κB in Tconv and Treg cells highlight the functional plasticity of the NF-κB signaling pathway and underscores the need for more selective strategies to therapeutically target NF-κB.



中文翻译:

NF-κB转录因子依赖性谱系特异性转录程序促进调节性T细胞的身份和功能。

传统的T(Tconv)细胞和调节性T(Treg)细胞均通过T细胞受体(TCR)复合物的连接被激活,从而导致转录因子NF-κB的诱导。在Tconv细胞中,NF-κB调节T细胞活化,增殖和功能所必需的基因的表达。然而,尚不清楚NF-κB在Treg功能中的作用。我们有条件地删除了发育中和成熟的Treg细胞中的典型NF-κB成员p65和c-Rel,发现它们具有独特但部分重复的作用。c-Rel对胸腺Treg的发育至关重要,而p65对于成熟的Treg身份和维持免疫耐受性至关重要。转录组和NF-κBp65结合分析表明,谱系特异性的NF-κB依赖性转录程序可通过增强的染色质可及性实现。

更新日期:2017-09-07
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