New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function.
New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function.
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DOI：
10.1186/s12929-017-0354-8
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发表时间：
2017-07-21
影响因子：
11
通讯作者：
Sytwu HK
中科院分区：
文献类型：
--
作者：
Fu SH;Yeh LT;Chu CC;Yen BL;Sytwu HK
B淋巴细胞诱导成熟蛋白-1（Blimp - 1）是产生抗体的B细胞发育和功能的主要调节因子。鉴于其在T淋巴细胞中的功能在过去十年内已被确定，我们回顾了近期的研究结果，重点关注其在T细胞发育、分化和功能过程中对基因表达的协同控制作用。Blimp - 1的表达主要局限于活化的T细胞，并且对于具有效应表型的一部分叉头框（Fox）p3⁺调节性T细胞产生白细胞介素（IL）- 10至关重要。Blimp - 1也是诱导胸腺中细胞清除以及关键调节外周T细胞活化和增殖所必需的。此外，Blimp - 1促进T辅助（Th）2细胞谱系定向，并限制Th1、Th17和滤泡辅助性T细胞分化。再者，Blimp - 1与其他转录因子协同调节效应T淋巴细胞中IL - 2、IL - 21和IL - 10的表达。在CD8⁺T细胞中，当它们遇到抗原时，在克隆扩增、分化、收缩和记忆形成阶段，不同群体中的Blimp - 1表达是不同的。而且，Blimp - 1在协调细胞因子受体信号网络和转录程序以调节效应和记忆CD8⁺T细胞的形成和功能及其耗竭的多个方面起着重要作用。Blimp - 1还作为T细胞活化和抑制的守门员，以预防或抑制自身免疫疾病、抗病毒反应和抗肿瘤免疫。在本综述中，我们讨论了Blimp - 1在调节T细胞命运和效应功能的基因网络复杂调控中的新兴作用，并为T淋巴细胞内稳态提供了一个以Blimp - 1为主导的转录框架。
B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3+ regulatory T cells with an effector phenotype. Blimp-1 is also required to induce cell elimination in the thymus and critically modulates peripheral T cell activation and proliferation. In addition, Blimp-1 promotes T helper (Th) 2 lineage commitment and limits Th1, Th17 and follicular helper T cell differentiation. Furthermore, Blimp-1 coordinates with other transcription factors to regulate expression of IL-2, IL-21 and IL-10 in effector T lymphocytes. In CD8+ T cells, Blimp-1 expression is distinct in heterogeneous populations at the stages of clonal expansion, differentiation, contraction and memory formation when they encounter antigens. Moreover, Blimp-1 plays a fundamental role in coordinating cytokine receptor signaling networks and transcriptional programs to regulate diverse aspects of the formation and function of effector and memory CD8+ T cells and their exhaustion. Blimp-1 also functions as a gatekeeper of T cell activation and suppression to prevent or dampen autoimmune disease, antiviral responses and antitumor immunity. In this review, we discuss the emerging roles of Blimp-1 in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis.
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