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Finding a way out: lymphocyte egress from lymphoid organs

Abstract

The egress of lymphocytes from the thymus and secondary lymphoid organs into circulatory fluids is essential for normal immune function. The discovery that a small-molecule inhibitor of lymphocyte exit, FTY720, is a ligand for sphingosine 1-phosphate (S1P) receptors led to studies demonstrating that S1P receptor type 1 (S1P1) is needed in T cells and B cells for their egress from lymphoid organs. S1P exists in higher concentrations in blood and lymph than in lymphoid organs, and this differential is also required for lymphocyte exit. Transcriptional and post-translational mechanisms regulate S1P1 and thus the egress of lymphocytes. In this review we discuss the body of evidence supporting a model in which lymphocyte egress is promoted by encounter with S1P at exit sites. We relate this model to work examining the effects of S1P receptor agonists on endothelium.

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Figure 1: Model of lymphocyte egress.
Figure 2: Physiological regulation of lymphocyte S1P1 expression.

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Acknowledgements

We thank L. Shiow for comments on the manuscript, and members of the Cyster lab for discussions. Supported by the Irvington Institute for Immunological Research (S.R.S.) and the Howard Hughes Medical Institute (J.G.C.).

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Correspondence to Susan R Schwab or Jason G Cyster.

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Schwab, S., Cyster, J. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol 8, 1295–1301 (2007). https://doi.org/10.1038/ni1545

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