Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Laboratory of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Cell Rep. 2019 Dec 24;29(13):4447-4459.e6. doi: 10.1016/j.celrep.2019.11.089.
Forkhead box protein P3 (FOXP3) regulatory T cells (T cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of T cells, while enforced MAZR expression impairs T cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic T cell development and during in-vitro-induced human T cell differentiation, suggesting that MAZR protein levels are critical for controlling T cell development. However, MAZR-deficient T cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral T cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a T cell-intrinsic transcriptional network that modulates T cell development.
叉头框蛋白 P3（FOXP3）调节性 T 细胞（T 细胞）在维持耐受和免疫平衡中发挥关键作用。在这里，我们报告称，转录因子 MAZR（也称为 PATZ1）的 T 细胞特异性缺失会导致 T 细胞频率增加，而强制表达 MAZR 则会损害 T 细胞分化。此外，MAZR 的表达水平在胸腺 T 细胞发育过程中和体外诱导的人类 T 细胞分化过程中逐渐下调，表明 MAZR 蛋白水平对于控制 T 细胞发育至关重要。然而，MAZR 缺陷型 T 细胞在体外仅表现出轻微的转录变化，表明 MAZR 对于建立外周 T 细胞的转录程序不是必需的。最后，MAZR 的缺失降低了葡聚糖硫酸钠（DSS）诱导的结肠炎的临床评分，表明 T 细胞中的 MAZR 活性控制了肠道炎症的程度。总之，这些数据表明 MAZR 是调节 T 细胞发育的 T 细胞内在转录网络的一部分。
