The Transporter Spns2 Is Required for Secretion of Lymph but Not Plasma Sphingosine-1-Phosphate

Alejandra Mendoza, Béatrice Bréart, Willy D. Ramos-Perez, Lauren A. Pitt, Michael Gobert, Manjula Sunkara, Juan J. Lafaille, Andrew J. Morris, Susan R. Schwab

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Plasma sphingosine-1-phosphate (S1P) regulates vascular permeability, and plasma and lymph S1P guide lymphocyte egress from lymphoid organs. S1P is made intracellularly, and little is known about how S1P is delivered into circulatory fluids. Here, we find that mice without the major facilitator superfamily transporter Spns2 have a profound reduction in lymph S1P, but only a minor decrease in plasma S1P. Spns2-deficient mice have a redistribution of lymphocytes from the spleen to lymph nodes and a loss of circulating lymphocytes, consistent with normal egress from the spleen directed by plasma S1P and blocked egress from lymph nodes directed by lymph S1P. Spns2 is needed in endothelial cells to supply lymph S1P and support lymphocyte circulation. As a differential requirement for lymph and blood S1P, Spns2 may be an attractive target for immune suppressive drugs.

Original languageEnglish
Pages (from-to)1104-1110
Number of pages7
JournalCell Reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012

Bibliographical note

Funding Information:
This work was supported by NIH grant R01AI085166 and an NYU Whitehead Fellowship (to S.R.S.), NIH grants R01GM50388 and P20RR021954 (to A.J.M.), NIH training grant T32-HD007520 (to A.M.), a Human Frontier Science Program Long-Term Fellowship (to B.B.), and NIH training grant T32-CA009161 (Levy, to W.D.R.P.). We thank Ken Cadwell, Jason Cyster, David Fooksman, Jason Hall, Sergei Koralov, MacLean Sellars, and Leslie Summers deLuca for critical comments on the manuscript.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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