Conserved and Unique Functions of Blimp1 in Immune Cells.
Conserved and Unique Functions of Blimp1 in Immune Cells.
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DOI：
10.3389/fimmu.2021.805260
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发表时间：
2021
影响因子：
7.3
通讯作者：
Martins GA
中科院分区：
文献类型：
--
作者：
Nadeau S;Martins GA
B淋巴细胞诱导成熟蛋白1（Blimp 1）是一种进化上保守的转录调节因子，最初被描述为基因转录的阻遏物。Blimp 1在包括免疫细胞在内的许多细胞谱系中至关重要地调节胚胎发育和终末分化。Blimp 1在免疫中作用的初步研究确定了其在淋巴细胞末端效应子分化和功能中的非冗余作用。在B细胞中，Blimp 1驱动浆母细胞形成和抗体分泌，而在T细胞中，Blimp 1调节功能分化，包括细胞因子基因表达。这些研究确定Blimp 1是一种重要的转录调节因子，可以促进有效和受控的适应性免疫。最近的研究也证明了Blimp 1在先天免疫细胞，特别是骨髓细胞中的重要作用，Blimp 1已被确定为树突状细胞成熟和T细胞引发的内在调节因子。新兴的研究已经确定了Blimp 1在不同免疫细胞亚群中的保守和独特功能，包括B细胞中Igh基因转录的独特直接激活以及B细胞、T细胞和骨髓细胞中与BCL 6的保守拮抗作用。此外，与编码Blimp 1（PRDM 1）的基因相关的多态性与人类的许多慢性炎症性疾病有关。Blimp 1已被证明通过与其他转录因子竞争结合靶基因座和/或通过募集促进抑制性染色质结构的各种染色质修饰辅因子（如组蛋白去乙酰化酶和甲基转移酶）来调节靶基因表达。此外，Blimp 1功能已被证明基本上是剂量和环境依赖性的，这增加了Blimp 1作为基因表达调节剂的多功能性。在这里，我们回顾了Blimp 1在免疫中的复杂作用，并强调了对这种转录调节因子生物学的理解中的特定差距，主要集中在可以促进对免疫系统中Blimp 1调节的新途径的描述和理解的方面。
B-lymphocyte-induced maturation protein-1 (Blimp1), is an evolutionarily conserved transcriptional regulator originally described as a repressor of gene transcription. Blimp1 crucially regulates embryonic development and terminal differentiation in numerous cell lineages, including immune cells. Initial investigations of Blimp1’s role in immunity established its non-redundant role in lymphocytic terminal effector differentiation and function. In B cells, Blimp1 drives plasmablast formation and antibody secretion, whereas in T cells, Blimp1 regulates functional differentiation, including cytokine gene expression. These studies established Blimp1 as an essential transcriptional regulator that promotes efficient and controlled adaptive immunity. Recent studies have also demonstrated important roles for Blimp1 in innate immune cells, specifically myeloid cells, and Blimp1 has been established as an intrinsic regulator of dendritic cell maturation and T cell priming. Emerging studies have determined both conserved and unique functions of Blimp1 in different immune cell subsets, including the unique direct activation of the igh gene transcription in B cells and a conserved antagonism with BCL6 in B cells, T cells, and myeloid cells. Moreover, polymorphisms associated with the gene encoding Blimp1 (PRDM1) have been linked to numerous chronic inflammatory conditions in humans. Blimp1 has been shown to regulate target gene expression by either competing with other transcription factors for binding to the target loci, and/or by recruiting various chromatin-modifying co-factors that promote suppressive chromatin structure, such as histone de-acetylases and methyl-transferases. Further, Blimp1 function has been shown to be essentially dose and context-dependent, which adds to Blimp1’s versatility as a regulator of gene expression. Here, we review Blimp1’s complex roles in immunity and highlight specific gaps in the understanding of the biology of this transcriptional regulator, with a major focus on aspects that could foster the description and understanding of novel pathways regulated by Blimp1 in the immune system.
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