title: Lipid phosphate phosphatase 3 enables efficient thymic egress.
abstract: The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for the loss of LPP3. Moreover, conditional deletion of LPP3 in either epithelial cells or endothelial cells is sufficient to inhibit egress. These results suggest that S1P generation and destruction are tightly regulated and that LPP3 is essential to establish the balance.
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: Béatrice
authors.initials: B
authors.lastname: Bréart
authors.forename: Willy D
authors.initials: WD
authors.lastname: Ramos-Perez
authors.forename: Alejandra
authors.initials: A
authors.lastname: Mendoza
authors.forename: Abdelghaffar K
authors.initials: AK
authors.lastname: Salous
authors.forename: Michael
authors.initials: M
authors.lastname: Gobert
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
authors.forename: Diana
authors.initials: D
authors.lastname: Escalante-Alcalde
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Susan R
authors.initials: SR
authors.lastname: Schwab
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000201:enzymology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D049452:Green Fluorescent Proteins; D037181:Lectins, C-Type; D008246:Lysophospholipids; D010711:Phosphatidate Phosphatase; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000081025:Sphingosine-1-Phosphate Receptors; D000099192:CD69 Antigens; C556330:S1pr1 protein, mouse; C060506:sphingosine 1-phosphate; C479566:Plpp3 protein, mouse