HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900678v1 183/6/3865    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Dong, Y. Articles by Tao, W. PubMed PubMed Citation Articles by Dong, Y. Articles by Tao, W.

A Cell-Intrinsic Role for Mst1 in Regulating Thymocyte Egress¹

Yongli Dong^*, Xingrong Du^*, Jian Ye^*, Min Han^*,, Tian Xu^*,, Yuan Zhuang^2,*, and Wufan Tao^2,*

^* Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai, China; Howard Hughes Medical Institute, Department of Molecular, Cell, and Developmental Biology, University of Colorado, Boulder, CO 80309; Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06536; and Department of Immunology, Duke University Medical Center, Durham, NC 27701

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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by Chinese Key Projects for Basic Research (973) Grant 2006CB806700, Hi-Tech Research and Development Project (863) Grant 2007AA022101, National Natural Science Foundation of China Grant 30630043, Key Projects Grant for Basic Research 08JC1400800 from the Science and Technology Committee of Shanghai Municipality, Shanghai Pujiang Program Grant 05PJ14024, and the 211 and 985 projects of the Chinese Ministry of Education.

² Address correspondence and reprint requests to Dr. Wufan Tao, Institute of Developmental Biology and Molecular Medicine, Fudan University, Shanghai 200433, the People’s Republic of China. E-mail address: Wufan_tao{at}fudan.edu.cn or Dr. Yuan Zhuang, Department of Immunology, Duke University Medical Center, Durham, NC 27701. E-mail address: yzhuang{at}duke.edu

³ Abbreviations used in this paper: S1P, sphingosine-1-phosphate; 7AAD, 7-amino actinomycin D; CMFDA, 5-chloromethylfluorescein diacetate; CMTMR, 5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine; DP, double positive; ES, embryonic stem; HET, heterozygous; HO, homozygous; PGK, phosphoglycerate kinase; S1P₁, S1P receptor 1; SP, single positive; WT, wild type.

⁴ The online version of this article contains supplemental material.