Sci. Immunol. 4, eaav1263 (2019)
Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking. In Science Immunology, Xiong et al. show that S1P receptors (S1PRs) serve distinct roles during the migration of CD4+ T cells across lymphatic endothelial cell (LEC) barriers into the afferent lymphatics. LECs express S1PR2, which responds to S1P by upregulating expression of the adhesion molecule VCAM-1 and altering expression of cellular junction proteins, including VE-cadherin, occludin and zonulin-1. Mouse and human CD4+ effector and memory T cells express S1PR1 and S1PR4. Inhibition or disruption of S1PR1, S1PR4 or S1PR2 diminishes the migration of T cells to S1P both in vitro and in vivo, but not their migration to the chemokine receptor CCR7 ligand CCL19. Inhibition of S1P signaling blunts early interactions of T cells with LECs, although S1PR1 seems to function differently from S1PR4. Interestingly, S1P-dependent signaling preferentially affects the transcellular migration of T cells through LECs rather than their paracellular trafficking. Thus, S1P governs distinct steps in the trafficking of T cells into the afferent lymphatics.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dempsey, L.A. Distinct S1PR roles. Nat Immunol 20, 517 (2019). https://doi.org/10.1038/s41590-019-0393-2
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41590-019-0393-2