Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Science. 2020 Mar 13;367(6483):1255-1260. doi: 10.1126/science.aax0194.
T cells maintain a quiescent state prior to activation. As inappropriate T cell activation can cause disease, T cell quiescence must be preserved. Despite its importance, the mechanisms underlying the "quiescent state" remain elusive. Here, we identify BTG1 and BTG2 (BTG1/2) as factors responsible for T cell quiescence. BTG1/2-deficient T cells show an increased proliferation and spontaneous activation due to a global increase in messenger RNA (mRNA) abundance, which reduces the threshold to activation. BTG1/2 deficiency leads to an increase in polyadenylate tail length, resulting in a greater mRNA half-life. Thus, BTG1/2 promote the deadenylation and degradation of mRNA to secure T cell quiescence. Our study reveals a key mechanism underlying T cell quiescence and suggests that low mRNA abundance is a crucial feature for maintaining quiescence.
T 细胞在激活前保持静止状态。由于不适当的 T 细胞激活会导致疾病，因此必须保持 T 细胞静止。尽管其重要性，但其“静止状态”的机制仍然难以捉摸。在这里，我们确定了 BTG1 和 BTG2（BTG1/2）是负责 T 细胞静止的因素。由于信使 RNA（mRNA）丰度的全面增加，BTG1/2 缺陷型 T 细胞表现出增殖增加和自发激活，这降低了激活的阈值。BTG1/2 缺乏会导致多聚腺苷酸尾巴长度增加，从而导致 mRNA 半衰期延长。因此，BTG1/2 促进 mRNA 的脱腺苷酸化和降解，以确保 T 细胞静止。我们的研究揭示了 T 细胞静止的关键机制，并表明低 mRNA 丰度是维持静止的关键特征。
