title: Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.
abstract: Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo.
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rieck
authors.affiliation: Molecular Genetics & Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kremser
authors.affiliation: Institute of Experimental Immunology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jobin
authors.affiliation: Institute of Experimental Immunology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mettke
authors.affiliation: Institute of Experimental Immunology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Center for Sepsis Control and Care (CSCC), and the Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Gräler
authors.affiliation: Molecular Genetics & Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D060168:Thymocytes / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; C580723:Cers2 protein, mouse; D051049:Sphingosine N-Acyltransferase; D013110:Sphingosine
keywords: Chemotaxis; Emigration; Lymphocytes; Sphingosine-1-phosphate; Thymus