Article
- The EMBO Journal (2009) 28, 1319 - 1331
- doi:10.1038/emboj.2009.82
Published online: 2 April 2009
Subject Categories:
Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes
Koko Katagiri1, Tomoya Katakai1, Yukihiko Ebisuno1, Yoshihiro Ueda1, Takaharu Okada2,3 and Tatsuo Kinashi1
- Department of Molecular Genetics, Kansai Medical University, Fumizono-cho, Moriguchi-City, Osaka, Japan
- Department of Synthetic Chemistry and Biological Chemistry, Innovative Techno-Hub for Integrated Medical Bio-imaging, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto, Japan
- Research Unit for Immunodynamics, RIKEN, Research Center for Allergy and Immunology, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan
Correspondence to:
Tatsuo Kinashi,
Corresponding author. Department of Molecular Genetics, Kansai Medical University, Fumizono-cho 10-15, Moriguchi-City, Osaka, 570-8506, Japan. Tel.: +81 6 6993 9445; Fax: +81 6 6994 6099;
E-mail: kinashi@takii.kmu.ac.jp
Received 4 December 2008; Accepted 3 March 2009
Abstract
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 
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.
Keywords:
- adhesion,
- LFA-1,
- migration,
- Mst1
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