Laboratory of Transcriptional Regulation, RIKEN Research Institute for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
Int Immunol. 2011 Nov;23(11):661-8. doi: 10.1093/intimm/dxr078. Epub 2011 Sep 23.
T lymphocytes, which are central players in orchestrating immune responses, consist of several subtypes with distinct functions. The thymus is an organ where hematopoietic progenitors undergo sequential developmental processes to give rise to this variety of T-cell subsets with diverse antigen specificity. In the periphery, naive T cells further differentiate into effector cells upon encountering antigens. There are several developmental checkpoints during T-cell development, where regulation by a combination of transcription factors imprints specific functional properties on precursors. The transcription factors E2A, GATA-binding protein 3 (Gata3) and RUNT-related transcription factor (Runx) are involved at various stages in the differentiation of double-negative thymocytes and in β-selection, as are transcription factors from the Notch signaling pathway; other transcription factors such as B-cell lymphoma/leukemia 11b (Bcl11b), myeloblastosis viral oncogene homolog (Myb) and inhibitor of DNA binding 3 (Id3) are involved at specific stages. Differentiation of T cells into helper versus cytotoxic cells involves not only antagonistic interplay between Runx and T(h) inducing POZ-Kruppel factor (ThPOK) but also complex interactions between MAZR, Gata3 and Myb in the activation and silencing of genes such as Cd4 and Cd8 as well as the gene that encodes ThPOK itself. A wide range of well-defined transcription factors, including signal transducer and activator of transcriptions (STATs), T-bet, Gata3, nuclear factor of activated T cell (NFAT), adaptor-related protein complex 1 (AP-1) and nuclear factor κB (NF-κB), are known to shape T(h)1/T(h)2 differentiation. Runx and Gata3 also operate in this process, as do c-Maf and recombining binding protein for immunoglobulin Jκ region (RBP-J) and the chromatin-reorganizing protein special AT-rich sequence-binding protein 1 (SATB1). In this review, we briefly discuss how T-cell characteristics are acquired and become divergent from the point of view of transcriptional regulation.
T 淋巴细胞是协调免疫反应的核心，由几种具有不同功能的亚型组成。胸腺是一个器官，造血祖细胞在那里经历连续的发育过程，产生具有不同抗原特异性的各种 T 细胞亚群。在外周，幼稚 T 细胞在遇到抗原时进一步分化为效应细胞。T 细胞发育过程中有几个发育检查点，其中转录因子的组合调节在祖细胞上印上特定的功能特性。转录因子 E2A、GATA 结合蛋白 3 (Gata3) 和 runt 相关转录因子 (Runx) 参与双阴性胸腺细胞的分化和 β 选择的各个阶段，Notch 信号通路的转录因子也是如此；其他转录因子，如 B 细胞淋巴瘤/白血病 11b (Bcl11b)、髓母细胞瘤病毒癌基因同源物 (Myb) 和 DNA 结合抑制因子 3 (Id3)，则在特定阶段参与。T 细胞向辅助细胞与细胞毒性细胞的分化不仅涉及 Runx 和 T(h)诱导 POZ-Kruppel 因子 (ThPOK) 的拮抗相互作用，还涉及 MAZR、Gata3 和 Myb 在激活和沉默 Cd4 和 Cd8 以及编码 ThPOK 本身的基因中的复杂相互作用。一系列明确的转录因子，包括信号转导和转录激活物 (STATs)、T-bet、Gata3、激活 T 细胞的核因子 (NFAT)、衔接蛋白相关蛋白复合物 1 (AP-1) 和核因子 κB (NF-κB)，已知可塑造 Th(h)1/Th(h)2 分化。Runx 和 Gata3 也在此过程中起作用，c-Maf 和免疫球蛋白 Jκ 区结合蛋白 (RBP-J) 以及染色质重排蛋白特殊富含 AT 序列结合蛋白 1 (SATB1) 也是如此。在这篇综述中，我们简要讨论了从转录调控的角度来看，T 细胞特征是如何获得并变得不同的。
