Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.
Institute for Maternal and Child Health-IRCCS "Burlo Garofolo" Trieste, Italy.
Immun Inflamm Dis. 2014 Dec;2(4):262-71. doi: 10.1002/iid3.44. Epub 2015 Jan 27.
Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown that MID1 is strongly up-regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant impact on exocytosis of lytic granules and the killing capacity of CTLs. The aims of the present study were to determine the localization of MID1 in migrating CTLs, and to investigate whether MID1 affects CTL polarization and migration. We found that MID1 mainly localizes to the uropod of migrating CTLs and that it has a substantial impact on CTL polarization and migration in vitro. Furthermore, analysis of contact hypersensitivity responses supported that MID1 controls effector functions of CTLs in hapten-challenged skin in vivo. These results provide significant new knowledge on the role of MID1 in CTL biology.
中线 1（MID1）是一种微管相关的泛素连接酶，可调节蛋白磷酸酶 2A 的水平。MID1 的功能丧失突变导致人类 X 连锁 Opitz G/BBB（OS）综合征，其特征是胚胎发生过程中线的发育缺陷。我们最近表明，MID1 在小鼠细胞毒性 T 淋巴细胞（CTL）中强烈上调，并且对细胞毒性颗粒的胞吐作用和 CTL 的杀伤能力有显著影响。本研究的目的是确定 MID1 在迁移 CTL 中的定位，并研究 MID1 是否影响 CTL 的极化和迁移。我们发现 MID1 主要定位于迁移 CTL 的尾足，并且对 CTL 的极化和体外迁移有重大影响。此外，对接触性过敏反应的分析支持 MID1 控制 CTL 在体内变应原挑战皮肤中的效应功能。这些结果为 MID1 在 CTL 生物学中的作用提供了重要的新知识。
