Nadeau Samantha, Martins Gislâine A
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute (IBIRI), Cedars-Sinai Medical Center (CSMC), Los Angeles, CA, United States.
Department of Biomedical Sciences, Research Division of Immunology, Cedars-Sinai Medical Center (CSMC), Los Angeles, CA, United States.
Front Immunol. 2022 Jan 27;12:805260. doi: 10.3389/fimmu.2021.805260. eCollection 2021.
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 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 () 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.
B淋巴细胞诱导成熟蛋白1(Blimp1)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抑制因子。Blimp1对包括免疫细胞在内的众多细胞谱系的胚胎发育和终末分化起着至关重要的调节作用。对Blimp1在免疫中作用的初步研究确立了其在淋巴细胞终末效应分化和功能中的非冗余作用。在B细胞中,Blimp1驱动浆母细胞形成和抗体分泌,而在T细胞中,Blimp1调节功能分化,包括细胞因子基因表达。这些研究确立了Blimp1作为促进高效且可控适应性免疫的重要转录调节因子的地位。最近的研究还证明了Blimp1在固有免疫细胞,特别是髓样细胞中的重要作用,并且Blimp1已被确立为树突状细胞成熟和T细胞启动的内在调节因子。新兴研究已经确定了Blimp1在不同免疫细胞亚群中的保守和独特功能,包括在B细胞中对基因转录的独特直接激活以及在B细胞、T细胞和髓样细胞中与BCL6的保守拮抗作用。此外,与编码Blimp1的基因()相关的多态性已与人类的多种慢性炎症性疾病相关联。已表明Blimp1通过与其他转录因子竞争结合靶位点,和/或通过招募各种促进抑制性染色质结构的染色质修饰辅助因子,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,已表明Blimp1的功能本质上是剂量和背景依赖性的,这增加了Blimp1作为基因表达调节因子的多功能性。在此,我们综述了Blimp1在免疫中的复杂作用,并强调了在理解这种转录调节因子生物学方面的特定空白,主要关注可能有助于描述和理解Blimp1在免疫系统中调节的新途径的方面。