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首页> 外文期刊>Molecular and Cellular Biology >Histone Acetyltransferase CBP Is Vital To Demarcate Conventional and Innate CD8+ T-Cell Development
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Histone Acetyltransferase CBP Is Vital To Demarcate Conventional and Innate CD8+ T-Cell Development

机译：组蛋白乙酰转移酶CBP对传统和先天CD8 + T细胞发育的界定至关重要

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Defining the chromatin modifications and transcriptional mechanisms that direct the development of different T-cell lineages is a major challenge in immunology. The transcriptional coactivators CREB binding protein (CBP) and the closely related p300, which comprise the KAT3 family of histone/protein lysine acetyltransferases, interact with over 50 T-lymphocyte-essential transcriptional regulators. We show here that CBP, but not p300, modulates the thymic development of conventional adaptive T cells versus those having unconventional innate functions. Conditional inactivation of CBP in the thymus yielded CD8 single-positive (SP) thymocytes with an effector-, memory-, or innate-like T-cell phenotype. In this regard, CD8 SP thymocytes in CBP mutant mice were phenotypically similar to those reported for Itk and Rlk protein tyrosine kinase mutants, including the increased expression of the T-cell master regulatory transcription factor eomesodermin (Eomes) and the interleukin-2 and -15 receptor beta chain (CD122) and an enhanced ability to rapidly produce gamma interferon. CBP was required for the expression of the Itk-dependent genes Egr2, Egr3, and Il2, suggesting that CBP helps mediate Itk-responsive transcription. CBP therefore defines a nuclear component of the signaling pathways that demarcate the development of innate and adaptive na?ve CD8+ T cells in the thymus.
机译：定义染色质修饰和转录机制，以指导不同的T细胞谱系的发展是免疫学的一大挑战。转录共激活因子CREB结合蛋白（CBP）和密切相关的p300（包含组蛋白/蛋白质赖氨酸乙酰转移酶的KAT3家族）与50多种T淋巴细胞必需的转录调节因子相互作用。我们在这里显示CBP，而不是p300，与具有非常规先天功能的那些相比，可调节常规适应性T细胞的胸腺发育。胸腺中 CBP 的条件失活产生具有效应子，记忆或先天性T细胞表型的CD8单阳性（SP）胸腺细胞。在这方面， CBP 突变小鼠中的CD8 SP胸腺细胞在表型上与报道的Itk和Rlk蛋白酪氨酸激酶突变体相似，包括T细胞主调节转录因子eomesodermin（Eomes）的表达增加。白介素2和-15受体β链（CD122）以及增强的快速产生伽马干扰素的能力。 CBP是表达Itk依赖性基因 Egr2 ， Egr3 和 Il2 所必需的，这表明CBP有助于介导Itk响应转录。因此，CBP定义了信号通路的核成分，该信号通路界定了胸腺中先天性和适应性幼稚CD8 + T细胞的发育。

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