Immunity
Volume 28, Issue 1, 18 January 2008, Pages 122-133
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Article
S1P1 Receptor Signaling Overrides Retention Mediated by Gαi-Coupled Receptors to Promote T Cell Egress

https://doi.org/10.1016/j.immuni.2007.11.017Get rights and content
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Summary

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 Gαi-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 Gαi-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.

Cited by (0)

2

Present address: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto, Japan.

3

Present address: Department of Medicine, University of California, San Francisco, CA 94143, USA.

4

Present address: University of California, San Diego, 9500 Gilman Drive, Pacific Hall Rm. 1220, La Jolla, CA 92093.