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Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity

机译:转录后T细胞基因调控以限制Tfh细胞和自身免疫

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摘要

T follicular helper (Tfh) cells are crucial to induce protective extrafollicular and germinal center antibody responses against protein antigens. Over the last decade, control of Tfh cell numbers has emerged as an important regulatory checkpoint which, when perturbed, may lead to production of autoantibodies. Recent progress in understanding how Tfh cells are kept limiting has revealed an important role for posttranscriptional control of gene expression mediated by microRNAs such as miR-17 similar to 92, miR-155 and miR-146a, and the RNA-binding proteins Roquin and Regnase. Additionally, T cell microRNAs dysregulated in patients with systemic lupus erythematosus have been shown to influence processes such as DNA hypomethylation, IL-2 and CCL5 secretion, and Treg function, which contribute to autoantibody formation and tissue damage.
机译:T卵泡辅助细胞(Tfh)对于诱导针对蛋白抗原的保护性滤泡外和生发中心抗体反应至关重要。在过去的十年中,对Tfh细胞数量的控制已成为重要的监管检查站,一旦受到干扰,可能会导致自身抗体的产生。在了解如何限制Tfh细胞的最新进展中,揭示了转录后控制由miRNA介导的基因表达的重要作用,例如与92,miR-155和miR-146a类似的miR-17,以及RNA结合蛋白Roquin和Regnase 。此外,已显示在系统性红斑狼疮患者中失调的T细胞microRNA会影响DNA低甲基化,IL-2和CCL5分泌以及Treg功能等过程,这些过程有助于自身抗体的形成和组织损伤。

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