CBP/p300 Drives the Differentiation of Regulatory T Cells through Transcriptional and Non-Transcriptional Mechanisms
CBP/p300 Drives the Differentiation of Regulatory T Cells through Transcriptional and Non-Transcriptional Mechanisms
复制标题
DOI：
10.1158/0008-5472.can-18-3622
复制
发表时间：
2019-08-01
期刊：
影响因子：
11.2
通讯作者：
Mounir, Zineb
中科院分区：
文献类型：
--
作者：
Castillo, Joseph;Wu, Esther;Mounir, Zineb
调节性 T 细胞 (Treg) 具有免疫抑制作用，会对癌症免疫疗法的反应产生负面影响。 CREB 结合蛋白 (CBP) 和 p300 是密切相关的乙酰转移酶和转录共激活因子。在这里，我们评估了 CBP/p300 调节 Treg 分化的机制以及滤泡性淋巴瘤中 CBP/p300 功能丧失突变的后果。转录和表观遗传分析鉴定了 Treg 分化所必需的一系列转录因子。质谱分析表明，CBP/p300 乙酰化前列环素合酶，后者通过改变 T 细胞和 B 细胞的促炎细胞因子分泌来调节 Treg 分化。在滤泡性淋巴瘤中观察到携带 CBP/p300 功能丧失突变的组织中 Treg 的存在减少。我们的研究结果为 CBP/p300 对 Treg 分化的调节提供了新的见解，对免疫景观的改变具有潜在的临床意义。意义：本研究提供了对 CBP/p300 在 Tregs 分化中的动态作用的见解，对滤泡性淋巴瘤免疫景观的改变具有潜在的临床意义。
Regulatory T cells (Treg) are immunosuppressive and negatively impact response to cancer immunotherapies. CREB-binding protein (CBP) and p300 are closely related acetyltransferases and transcriptional coactivators. Here, we evaluate the mechanisms by which CBP/p300 regulate Treg differentiation and the consequences of CBP/p300 loss-of-function mutations in follicular lymphoma. Transcriptional and epigenetic profiling identified a cascade of transcription factors essential for Treg differentiation. Mass spectrometry analysis showed that CBP/p300 acetylates prostacyclin synthase, which regulates Treg differentiation by altering proinflammatory cytokine secretion by T and B cells. Reduced Treg presence in tissues harboring CBP/p300 loss-of-function mutations was observed in follicular lymphoma. Our findings provide novel insights into the regulation of Treg differentiation by CBP/p300, with potential clinical implications on alteration of the immune landscape.Significance: This study provides insights into the dynamic role of CBP/p300 in the differentiation of Tregs, with potential clinical implications in the alteration of the immune landscape in follicular lymphoma.