Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.
Faculty of Science, Charles University, Prague, Czechia.
Front Immunol. 2021 Apr 27;12:618332. doi: 10.3389/fimmu.2021.618332. eCollection 2021.
LST1 is a small adaptor protein expressed in leukocytes of myeloid lineage. Due to the binding to protein tyrosine phosphatases SHP1 and SHP2 it was thought to have negative regulatory function in leukocyte signaling. It was also shown to be involved in cytoskeleton regulation and generation of tunneling nanotubes. gene is located in MHCIII locus close to many immunologically relevant genes. In addition, its expression increases under inflammatory conditions such as viral infection, rheumatoid arthritis and inflammatory bowel disease and its deficiency was shown to result in slightly increased sensitivity to influenza infection in mice. However, little else is known about its role in the immune system homeostasis and immune response. Here we show that similar to humans, LST1 is expressed in mice in the cells of the myeloid lineage. , its deficiency results in alterations in multiple leukocyte subset abundance in steady state and under inflammatory conditions. Moreover, LST1-deficient mice show significant level of resistance to dextran sodium sulphate (DSS) induced acute colitis, a model of inflammatory bowel disease. These data demonstrate that LST1 regulates leukocyte abundance in lymphoid organs and inflammatory response in the gut.
LST1 是一种在髓系白细胞中表达的小衔接蛋白。由于与蛋白酪氨酸磷酸酶 SHP1 和 SHP2 结合，它被认为在白细胞信号转导中具有负调节功能。它还被证明参与细胞骨架调节和形成隧道纳米管。该基因位于 MHCIII 基因座附近，靠近许多免疫相关基因。此外，其表达在病毒感染、类风湿性关节炎和炎症性肠病等炎症条件下增加，其缺乏导致小鼠对流感感染的敏感性略有增加。然而，关于其在免疫系统稳态和免疫反应中的作用知之甚少。在这里，我们表明，与人类相似，LST1 在小鼠的髓系细胞中表达。 ，其缺乏导致在稳态和炎症条件下多种白细胞亚群丰度的改变。此外，LST1 缺陷小鼠对葡聚糖硫酸钠 (DSS) 诱导的急性结肠炎具有显著的抵抗力，这是一种炎症性肠病模型。这些数据表明 LST1 调节淋巴器官中的白细胞丰度和肠道中的炎症反应。
