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.

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。