Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium.
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+CD8alphabeta 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 CD8alphabeta naive lymphocytes originating from SP thymocytes express high levels of type 1 S1P receptor (S1P(1)), 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 TCRalphabeta or TCRgammadelta 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 S1P(1) expression or disruption of the S1P gradient halted conventional CD4 or CD8alphabeta 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.
Kunisawa
Jun
J
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Kurashima
Yosuke
Y
Higuchi
Morio
M
Gohda
Masashi
M
Ishikawa
Izumi
I
Ogahara
Ikuko
I
Kim
Namju
N
Shimizu
Miki
M
Kiyono
Hiroshi
H
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D004848:Epithelium / Q000276:immunology; D005260:Female; D000068876:Fingolimod Hydrochloride; D007422:Intestines / Q000166:cytology* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011409:Propylene Glycols / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D008246:Lysophospholipids; D011409:Propylene Glycols; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine