Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus
Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus
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DOI：
10.1038/ncomms2105
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发表时间：
2012-10-01
影响因子：
16.6
通讯作者：
Kinashi, Tatsuo
中科院分区：
文献类型：
--
作者：
Ueda, Yoshihiro;Katagiri, Koko;Kinashi, Tatsuo
胸腺细胞运输在胸腺选择中起重要作用。在这里，我们表明，海马同源MST 1是胸腺细胞迁移和抗原识别所需的LFA-1和ICAM-1的髓质内。使用胸腺组织的双光子成像，我们发现在负选择环境中，在罕见的Aire（+）ICAM-1（hi）髓质胸腺上皮细胞群附近，高度运动的成熟胸腺细胞被阻滞和激活。值得注意的是，Mst 1缺陷或阻断细胞粘附分子LFA-1和ICAM-1导致髓质内CD 4（+）胸腺细胞的迁移和抗原识别效率低下。与这些缺陷相一致，Mst 1（-/-）小鼠的胸腺细胞选择受损，在多个器官中显示T细胞依赖性炎症浸润并产生自身抗体。我们的研究结果表明，Mst 1在调节胸腺细胞自身抗原识别在髓质中的关键作用。
Thymocyte trafficking has an important role in thymic selection. Here we show that the Hippo homologue Mst1 is required for thymocyte migration and antigen recognition by LFA-1 and ICAM-1 within the medulla. Using two-photon imaging of thymic tissues, we found that highly motile mature thymocytes arrest and are activated in the vicinity of rare populations of Aire(+) ICAM-1(hi) medullary thymic epithelia in a negatively selecting environment. Notably, Mst1 deficiency or blocking the cell adhesion molecules LFA-1 and ICAM-1 results in inefficient migration and antigen recognition of CD4(+) thymocytes within the medulla. Consistent with these defects, thymocyte selection is impaired in Mst1(-/-)mice, which display T cell-dependent inflammatory infiltrates in multiple organs and develop autoantibodies. Our results suggest that Mst1 has a key role in regulating thymocyte self-antigen recognition in the medulla.