The Journal of Experimental Medicine
Avanti Polar Lipids
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Published online September 17, 2007
doi:10.1084/jem.20062446
The Journal of Experimental Medicine, Vol. 204, No. 10, 2335-2348
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Kunisawa et al.
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ARTICLE

 Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium

Jun Kunisawa1,2, Yosuke Kurashima1,2, Morio Higuchi1,2, Masashi Gohda1,2, Izumi Ishikawa1,2, Ikuko Ogahara1,2, Namju Kim1,2, Miki Shimizu1,2, and Hiroshi Kiyono1,2

1 Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
2 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 322-0012, Japan

CORRESPONDENCE Hiroshi Kiyono:kiyono{at}ims.u-tokyo.ac.jp

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+CD8{alpha}ß 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 CD8{alpha}ß 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 TCR{alpha}ß or TCR{gamma}{delta} 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 CD8{alpha}ß 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.

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.


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