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Immunity. 2008 Jan;28(1):122-33. doi: 10.1016/j.immuni.2007.11.017. Epub 2007 Dec 27.

S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress.

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1
Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.

Abstract

The mechanism by which sphingosine-1-phosphate receptor-1 (S1P1) acts to promote lymphocyte egress from lymphoid organs is not defined. Here, we showed that CCR7-deficient T cells left lymph nodes more rapidly than wild-type cells did, whereas CCR7-overexpressing cells were retained for longer. After treatment with FTY720, an agonist that causes downmodulation of lymphocyte S1P1, CCR7-deficient T cells were less effectively retained than wild-type T cells. Moreover, treatment with pertussis toxin to inactivate signaling via G alpha i-protein-coupled receptors restored egress competence to S1P1-deficient lymphocytes. We also found that T cell accumulation in lymph node cortical sinusoids required intrinsic S1P1 expression and was antagonized by CCR7. These findings suggest a model where S1P1 acts in the lymphocyte to promote lymph node egress by overcoming retention signals mediated by CCR7 and additional G alpha i-coupled receptors. Furthermore, by simultaneously upregulating S1P1 and downregulating CCR7, T cells that have divided multiple times switch to a state favoring egress over retention.

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PMID:
18164221
PMCID:
PMC2691390
DOI:
10.1016/j.immuni.2007.11.017
[Indexed for MEDLINE]
Free PMC Article

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