A Cell-Intrinsic Role for Mst1 in Regulating Thymocyte Egress
A Cell-Intrinsic Role for Mst1 in Regulating Thymocyte Egress
复制标题
Mst1 在调节胸腺细胞流出中的细胞内在作用
DOI：
10.4049/jimmunol.0900678
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发表时间：
2009-09-15
影响因子：
4.4
通讯作者：
Tao, Wufan
中科院分区：
文献类型：
--
作者：
Dong, Yongli;Du, Xingrong;Tao, Wufan
MST 1激酶最近被鉴定为在促进由趋化因子和TCR信号刺激的淋巴细胞极化和粘附中起重要作用。然而，在胸腺细胞发育的Mst 1通路的生理相关性还没有完全理解。在这项研究中，我们分析了Mst 1中断对胸腺细胞发育和迁移的影响。Mst 1缺陷（Mst 1（-/-））小鼠表现出胸腺中成熟胸腺细胞的积累，血液和外周淋巴组织中淋巴细胞的急剧减少，以及归巢到外周淋巴结的能力下降。Mst 1（-/-）胸腺细胞对趋化因子（如CCL 19）的趋化反应受损，但对鞘氨醇-1-磷酸的趋化反应未受损。对Mst 1（-/-）小鼠的进一步分析显示，成熟T细胞从胸腺中排出严重受损。T细胞系特异性敲除Mst 1基因证明了Mst 1在调节T细胞发育中的细胞内在作用。我们的研究表明，Mst 1是至关重要的控制淋巴细胞趋化性和胸腺细胞迁移。免疫学杂志，2009，183：3865-3872。
The MST1 kinase was recently identified as playing an essential role in the promotion of lymphocyte polarization and adhesion stimulated by chemokines and TCR signaling. However, the physiological relevance of the Mst1 pathway in thymocyte development is not completely understood. In this study, we analyzed the effect of Mst1 disruption on thymocyte development and migration. Mst1-deficient (Mst1(-/-)) mice displayed an accumulation of mature thymocytes in the thymus, a dramatic reduction of lymphocytes in blood and peripheral lymphoid tissues, and a decrease of homing ability to peripheral lymph nodes. Mst1(-/-) thymocytes were impaired in chemotactic response to chemokines, such as CCL19, but not to sphingosine-1-phosphate. Further analyses of Mst1(-/-) mice revealed a severe impairment in the egress of mature T cells from the thymus. T lineage-specific knockout of the Mst1 gene demonstrates a cell-intrinsic role for Mst1 in regulating T cell development. Our study indicates that Mst1 is crucial in controlling lymphocyte chemotaxis and thymocyte emigration. The Journal of Immunology, 2009, 183: 3865-3872.