title: The transporter Spns2 is required for secretion of lymph but not plasma sphingosine-1-phosphate.
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.
authors.affiliation: Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Mendoza
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bréart
authors.forename: Willy D
authors.initials: WD
authors.lastname: Ramos-Perez
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Pitt
authors.forename: Michael
authors.initials: M
authors.lastname: Gobert
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Susan R
authors.initials: SR
authors.lastname: Schwab
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D008196:Lymph / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008246:Lysophospholipids / Q000097:blood / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C572630:Spns2 protein, mouse; C060506:sphingosine 1-phosphate; D013110:Sphingosine