Ichimiya Shingo, Kamekura Ryuta, Kawata Koji, Kamei Motonari, Himi Tetsuo
Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Hum Genet. 2017 Jan;62(1):81-86. doi: 10.1038/jhg.2016.88. Epub 2016 Aug 4.
T follicular helper cells (Tfh cells), which are a prototypic subset of effector CD4 T cells, regulate the production of high-affinity antibodies by controlling B cells at initial and recall phases. Since the discovery of Tfh cells in human tonsils, many notable studies focusing on Tfh cells have clarified mechanisms underlying Tfh-cell-related physiological and pathological settings. Results of these studies revealed a chief regulatory function of BCL6 in Tfh cells and the involvement of Tfh cells in the pathogenesis of various disorders including autoimmune diseases, allergies and cancers. Further, accumulating evidence has revealed microRNAs (miRNAs) of functional noncoding RNAs (ncRNAs) to be cardinal regulators of Tfh cells during the processes of development, differentiation and plasticity. In this review article, we summarize and discuss the results of recent studies about miRNAs operating Tfh-cell function and their relationships in diseases. Through the window of such functional ncRNAs, the functional significance of Tfh cells in CD4 T-cell biology is becoming apparent. Studies to determine the complex background of the genetic program of Tfh cells operated by functional RNAs should lead to an understanding of the manifestations of Tfh cells with unidentified pathophysiological relevance.
滤泡辅助性T细胞（Tfh细胞）是效应性CD4 T细胞的一个典型亚群，通过在初始阶段和再次免疫阶段控制B细胞来调节高亲和力抗体的产生。自从在人类扁桃体中发现Tfh细胞以来，许多聚焦于Tfh细胞的显著研究已经阐明了Tfh细胞相关生理和病理状态的潜在机制。这些研究结果揭示了BCL6在Tfh细胞中的主要调节功能，以及Tfh细胞参与包括自身免疫性疾病、过敏和癌症在内的各种疾病的发病机制。此外，越来越多的证据表明，功能性非编码RNA（ncRNA）中的微小RNA（miRNA）在Tfh细胞的发育、分化和可塑性过程中是关键调节因子。在这篇综述文章中，我们总结并讨论了关于调控Tfh细胞功能的miRNA及其在疾病中的关系的近期研究结果。通过这种功能性ncRNA的窗口，Tfh细胞在CD4 T细胞生物学中的功能意义正变得日益明显。确定由功能性RNA操作的Tfh细胞遗传程序的复杂背景的研究，应该会有助于理解具有不明病理生理相关性的Tfh细胞的表现。
