Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, USA.
Biomedical Sciences Graduate Program, Columbus, OH, USA.
Immunol Rev. 2021 Mar;300(1):82-99. doi: 10.1111/imr.12936. Epub 2020 Dec 17.
Ikaros zinc finger transcription factors are important regulators of the gene programs underlying the development of hematopoietic cell lineages. The family consists of five members: Ikaros, Helios, Aiolos, Eos, and Pegasus, which engage in both homo- and heterotypic intrafamilial interactions to exert diverse functional effects. Pioneering studies focused on the role of these factors in early lymphoid development, as their absence resulted in severe defects in lymphocyte populations. More recent work has now begun to define nuanced, stage-specific roles for Ikaros family members in the differentiation and function of mature T, B, and innate lymphoid cell populations including natural killer (NK) cells. The precise transcriptional mechanisms by which these factors function, both independently and collaboratively, is an area of active investigation. However, several key themes appear to be emerging regarding the pathways influenced by Ikaros family members, including the end-to-end regulation of cytokine signaling. Here, we review roles for Ikaros factors in lymphoid cell development, differentiation, and function, including a discussion of the current understanding of the transcriptional mechanisms they employ and considerations for the future study of this important transcription factor family.
Ikaros 锌指转录因子是调控造血细胞谱系发育相关基因程序的重要调控因子。该家族由五个成员组成:Ikaros、Helios、Aiolos、Eos 和 Pegasus,它们通过同型和异型家族内相互作用发挥多种功能效应。开创性的研究集中在这些因子在早期淋巴细胞发育中的作用,因为它们的缺失导致淋巴细胞群体严重缺陷。最近的研究工作开始定义 Ikaros 家族成员在成熟 T、B 和固有淋巴细胞群体(包括自然杀伤 (NK) 细胞)的分化和功能中的细微、阶段特异性作用。这些因子独立和协作发挥功能的精确转录机制是一个活跃研究的领域。然而,关于受 Ikaros 家族成员影响的途径,似乎出现了几个关键主题,包括细胞因子信号的端到端调节。在这里,我们综述了 Ikaros 因子在淋巴细胞发育、分化和功能中的作用,包括对它们所采用的转录机制的当前理解的讨论,并考虑了对这个重要转录因子家族的未来研究。