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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-28
pubmed:abstractText
Sphingosine 1-phosphate (S1P) and its receptor, S1P receptor type 1 (S1P(1)), are essential for lymphocyte egress from secondary lymphoid organs (SLO). Fingolimod (FTY720), the S1P receptor modulator, inhibits lymphocyte egress from SLO and decreases circulating lymphocytes; however, it also induces a significant decrease in the number of peripheral blood lymphocytes in alymphoplasia (aly/aly) mice lacking SLO. In this study, we demonstrated that the administration of FTY720 induced sequestration of mature lymphocytes, particularly T cells, into the bone marrow (BM) in aly/aly mice, implying that the reduction of circulating lymphocytes in these mice by FTY720 was due to inhibition of lymphocyte egress from the BM. Since sequestration of mature T cells into the BM was also induced in normal mice by selective S1P(1) agonist or S1P lyase inhibitor, it is suggested that S1P(1) expression and the S1P gradient play an important role in egress of mature T cells from the BM. Prophylactic administration of FTY720 to ovalbumin (OVA)-immunized mice significantly inhibited footpad swelling induced by OVA challenging with a marked reduction of OVA-specific T(h) cells in the BM, indicating that immunomodulation by FTY720 is likely due to reduced circulation of antigen-specific T(h) cells. On the other hand, OVA-specific T(h) cells, like naive T cells, were also sequestered into the BM and SLO of OVA-immunized mice by a short exposure of FTY720 after OVA challenging. These results suggest that the S1P-S1P(1) axis plays a regulatory role in egress of mature T cells including antigen-specific T(h) cells from the BM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2377
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
515-25
pubmed:meshHeading
pubmed-meshheading:20497959-Adoptive Transfer, pubmed-meshheading:20497959-Animals, pubmed-meshheading:20497959-Bone Marrow, pubmed-meshheading:20497959-Cell Count, pubmed-meshheading:20497959-Cell Movement, pubmed-meshheading:20497959-Hypersensitivity, Delayed, pubmed-meshheading:20497959-Immunization, pubmed-meshheading:20497959-Lymphoid Tissue, pubmed-meshheading:20497959-Lysophospholipids, pubmed-meshheading:20497959-Male, pubmed-meshheading:20497959-Mice, pubmed-meshheading:20497959-Mice, Inbred C57BL, pubmed-meshheading:20497959-Mice, Mutant Strains, pubmed-meshheading:20497959-Ovalbumin, pubmed-meshheading:20497959-Oxadiazoles, pubmed-meshheading:20497959-Propylene Glycols, pubmed-meshheading:20497959-Receptors, Lysosphingolipid, pubmed-meshheading:20497959-Sphingosine, pubmed-meshheading:20497959-T-Lymphocytes, pubmed-meshheading:20497959-Thiophenes
pubmed:year
2010
pubmed:articleTitle
Sphingosine 1-phosphate receptor type 1 regulates egress of mature T cells from mouse bone marrow.
pubmed:affiliation
Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa, Japan.
pubmed:publicationType
Journal Article