Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes
Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes
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DOI：
10.1038/emboj.2009.82
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发表时间：
2009-05-06
期刊：
影响因子：
11.4
通讯作者：
Kinashi, Tatsuo
中科院分区：
文献类型：
--
作者：
Katagiri, Koko;Katakai, Tomoya;Kinashi, Tatsuo
淋巴细胞粘附和迁移的调节在免疫监视过程中淋巴细胞运输中起着至关重要的作用。然而，我们对调节这些过程的细胞内信号传导的理解仍然有限。在这里，我们证明 Ste20 样激酶 Mst1 在体内淋巴细胞运输中发挥着至关重要的作用。 Mst1(-/-)淋巴细胞表现出与高内皮小静脉的牢固粘附受损，导致归巢能力低下。生理剪切流下的体外淋巴细胞粘附级联试验表明，Mst1(-/-)淋巴细胞在内皮上的停留时间显着减少，而其L-选择素依赖性滚动/束缚和向LFA-1介导的停滞的转变不受影响。 Mst1(-/-)淋巴细胞在通过α4整合素稳定粘附方面也存在缺陷。因此，Mst1(-/-)小鼠的外周淋巴组织营养不良，脾脏边缘区B细胞和树突状细胞减少，单个阳性胸腺细胞迁移有缺陷。此外，Mst1(-/-)淋巴细胞在淋巴结源性基质细胞和淋巴结内的运动能力受损。因此，我们的数据表明 Mst1 是参与淋巴细胞进入和间质迁移的关键酶。 EMBO 杂志 (2009) 28, 1319-1331。 doi：10.1038/emboj.2009.82； 2009 年 4 月 2 日在线发布
The regulation of lymphocyte adhesion and migration plays crucial roles in lymphocyte trafficking during immunosurveillance. However, our understanding of the intracellular signalling that regulates these processes is still limited. Here, we show that the Ste20-like kinase Mst1 plays crucial roles in lymphocyte trafficking in vivo. Mst1(-/-) lymphocytes exhibited an impairment of firm adhesion to high endothelial venules, resulting in an inefficient homing capacity. In vitro lymphocyte adhesion cascade assays under physiological shear flow revealed that the stopping time of Mst1(-/-) lymphocytes on endothelium was markedly reduced, whereas their L-selectin-dependent rolling/tethering and transition to LFA-1-mediated arrest were not affected. Mst1(-/-) lymphocytes were also defective in the stabilization of adhesion through alpha 4 integrins. Consequently, Mst1(-/-) mice had hypotrophic peripheral lymphoid tissues and reduced marginal zone B cells and dendritic cells in the spleen, and defective emigration of single positive thymocytes. Furthermore, Mst1(-/-) lymphocytes had impaired motility over lymph node-derived stromal cells and within lymph nodes. Thus, our data indicate that Mst1 is a key enzyme involved in lymphocyte entry and interstitial migration. The EMBO Journal (2009) 28, 1319-1331. doi: 10.1038/emboj.2009.82; Published online 2 April 2009