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
Affiliations
Alejandra Mendoza
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Béatrice Bréart
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Willy D. Ramos-Perez
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Lauren A. Pitt
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Michael Gobert
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Manjula Sunkara
Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, 40536, USA
Juan J. Lafaille
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Andrew J. Morris
Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, 40536, USA
Susan R. Schwab
Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
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.
