It is well established that intraepithelial T lymphocytes (IELs) are derived from conventional single-positive (SP) thymocytes, as well as unconventional double-negative (DN) thymocytes and CD103+CD8αβ recent thymic emigrants (RTEs). We show that IELs can be divided into two groups according to their dependency on sphingosine 1-phosphate (S1P) for trafficking into the intestines. CD4 or CD8αβ naive lymphocytes originating from SP thymocytes express high levels of type 1 S1P receptor (S1P1), and their preferential migration into the large intestine is regulated by S1P. In contrast, RTEs migrate exclusively into the small intestine, whereas DN thymic IEL precursors expressing either TCRαβ or TCRγδ migrate into both the small and large intestines. S1P does not play a role in the migration pathways of these unconventional thymic IEL precursors. Thus, down-regulation of S1P1 expression or disruption of the S1P gradient halted conventional CD4 or CD8αβ IEL trafficking into the intestines, but did not affect the trafficking of unconventional thymic IEL precursors. These data are the first to demonstrate that a lipid-mediated system discriminates IELs originating from conventional and unconventional thymic precursors.
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1 October 2007
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September 17 2007
Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium
Jun Kunisawa,
Jun Kunisawa
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Yosuke Kurashima,
Yosuke Kurashima
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Morio Higuchi,
Morio Higuchi
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Masashi Gohda,
Masashi Gohda
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Izumi Ishikawa,
Izumi Ishikawa
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Ikuko Ogahara,
Ikuko Ogahara
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Namju Kim,
Namju Kim
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Miki Shimizu,
Miki Shimizu
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Hiroshi Kiyono
Hiroshi Kiyono
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
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Jun Kunisawa
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Yosuke Kurashima
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Morio Higuchi
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Masashi Gohda
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Izumi Ishikawa
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Ikuko Ogahara
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Namju Kim
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Miki Shimizu
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
Hiroshi Kiyono
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan
CORRESPONDENCE Hiroshi Kiyono:[email protected]
Abbreviations used: CCR9, CC chemokine receptor 9; CP, colonic patch; DN, double-negative; DOP, deoxypyridoxine; DP, double-positive; EC, epithelial cell; IEL, intraepithelial T lymphocyte; IBD, inflammatory bowel disease; MLN, mesenteric LN; PP, Peyer's patch; RTE, recent thymic emigrant; S1P, sphingosine 1-phosphate; S1P1, type 1 S1P receptor; SLN, sacral LN; SP, single-positive; z TN, triple-negative; TP, triple-positive.
Received:
November 21 2006
Accepted:
August 15 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (10): 2335–2348.
Article history
Received:
November 21 2006
Accepted:
August 15 2007
Citation
Jun Kunisawa, Yosuke Kurashima, Morio Higuchi, Masashi Gohda, Izumi Ishikawa, Ikuko Ogahara, Namju Kim, Miki Shimizu, Hiroshi Kiyono; Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium . J Exp Med 1 October 2007; 204 (10): 2335–2348. doi: https://doi.org/10.1084/jem.20062446
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