{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:47:05Z","timestamp":1780566425055,"version":"3.54.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIDDK108670"],"award-info":[{"award-number":["NIDDK108670"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BLRD VA","award":["1I01BX003436"],"award-info":[{"award-number":["1I01BX003436"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,6]]},"abstract":"<jats:p>Sphingosine-1-phosphate (S1P) receptor agonists are a promising therapeutic alternative to anti-integrin antibodies in inflammatory bowel disease. Here, we report that modulation of tissue S1P levels via inhibition of the S1P lyase might be an effective alternative, acting by interference with thymocyte maturation.<\/jats:p>","DOI":"10.1093\/ibd\/izz174","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T04:03:26Z","timestamp":1575605006000},"page":"216-228","source":"Crossref","is-referenced-by-count":28,"title":["Sphingosine-1-Phosphate Lyase Inhibition Alters the S1P Gradient and Ameliorates Crohn\u2019s-Like Ileitis by Suppressing Thymocyte Maturation"],"prefix":"10.1093","volume":"26","author":[{"given":"Thangaraj","family":"Karuppuchamy","sequence":"first","affiliation":[{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"},{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Tyler","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"},{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke R","family":"Lundborg","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"},{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"P\u00e9rez-Jeldres","sequence":"additional","affiliation":[{"name":"Universidad Cat\u00f3lica de Chile, Santiago, Chile"},{"name":"Hospital San Borja Arriar\u00e1n, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail K","family":"Kimball","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Aurora, Colorado, USA"},{"name":"Department of Pathology, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T","family":"Clambey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Aurora, Colorado, USA"},{"name":"Department of Pathology, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Jedlicka","sequence":"additional","affiliation":[{"name":"Department of Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Rivera-Nieves","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA"},{"name":"Gastroenterology Section, San Diego VA Medical Center, La Jolla Village Drive, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,6]]},"reference":[{"key":"2020010604480006500_CIT0001","doi-asserted-by":"crossref","first-page":"S631","DOI":"10.1093\/ecco-jcc\/jjy067","article-title":"Targeting leukocyte traffic: a new era for the treatment of inflammatory bowel disease","volume":"12","author":"Rivera-Nieves","year":"2018","journal-title":"J Crohns Colitis."},{"key":"2020010604480006500_CIT0002","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa020732","article-title":"Natalizumab for active Crohn\u2019s disease","volume":"348","author":"Ghosh","year":"2003","journal-title":"N Engl J Med."},{"key":"2020010604480006500_CIT0003","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1215734","article-title":"Vedolizumab as induction and maintenance therapy for ulcerative colitis","volume":"369","author":"Feagan","year":"2013","journal-title":"N Engl J Med."},{"key":"2020010604480006500_CIT0004","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.med.080708.082655","article-title":"Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies","volume":"61","author":"Major","year":"2010","journal-title":"Annu Rev Med."},{"key":"2020010604480006500_CIT0005","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.immunol.23.021704.115628","article-title":"Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs","volume":"23","author":"Cyster","year":"2005","journal-title":"Annu Rev Immunol."},{"key":"2020010604480006500_CIT0006","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"Matloubian","year":"2004","journal-title":"Nature."},{"key":"2020010604480006500_CIT0007","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1126\/science.1113640","article-title":"Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients","volume":"309","author":"Schwab","year":"2005","journal-title":"Science."},{"key":"2020010604480006500_CIT0008","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nri2400","article-title":"The alliance of sphingosine-1-phosphate and its receptors in immunity","volume":"8","author":"Rivera","year":"2008","journal-title":"Nat Rev Immunol."},{"key":"2020010604480006500_CIT0009","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1056\/NEJMoa1513248","article-title":"Ozanimod induction and maintenance treatment for ulcerative colitis","volume":"374","author":"Sandborn","year":"2016","journal-title":"N Engl J Med."},{"key":"2020010604480006500_CIT0010","first-page":"299","article-title":"Ubiquitination of G-protein-coupled receptors","volume":"259","author":"Marchese","year":"2004","journal-title":"Methods Mol Biol."},{"key":"2020010604480006500_CIT0011","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nchembio.547","article-title":"Actions of a picomolar short-acting S1P1 agonist in S1P1-eGFP knock-in mice","volume":"7","author":"Cahalan","year":"2011","journal-title":"Nat Chem Biol."},{"key":"2020010604480006500_CIT0012","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.advenzreg.2009.10.024","article-title":"Sphingosine 1-phosphate lyase, a key regulator of sphingosine 1-phosphate signaling and function","volume":"50","author":"Serra","year":"2010","journal-title":"Adv Enzyme Regul."},{"key":"2020010604480006500_CIT0013","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1194\/jlr.M034108","article-title":"S1P1 localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity","volume":"54","author":"Montrose","year":"2013","journal-title":"J Lipid Res."},{"key":"2020010604480006500_CIT0014","doi-asserted-by":"crossref","first-page":"47281","DOI":"10.1074\/jbc.M306896200","article-title":"Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability","volume":"278","author":"Sanchez","year":"2003","journal-title":"J Biol Chem."},{"key":"2020010604480006500_CIT0015","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1042\/bj3300605","article-title":"Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1","volume":"330 (Pt 2)","author":"Zondag","year":"1998","journal-title":"Biochem J."},{"key":"2020010604480006500_CIT0016","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1146\/annurev.biochem.78.072407.103733","article-title":"Sphingosine 1-phosphate receptor signaling","volume":"78","author":"Rosen","year":"2009","journal-title":"Annu Rev Biochem."},{"key":"2020010604480006500_CIT0017","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.chemphyslip.2015.07.007","article-title":"Inhibitors of sphingosine-1-phosphate metabolism (sphingosine kinases and sphingosine-1-phosphate lyase)","volume":"197","author":"Sanlleh\u00ed","year":"2016","journal-title":"Chem Phys Lipids."},{"key":"2020010604480006500_CIT0018","doi-asserted-by":"crossref","first-page":"8650","DOI":"10.1021\/jm101183p","article-title":"Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932)","volume":"53","author":"Bagdanoff","year":"2010","journal-title":"J Med Chem."},{"key":"2020010604480006500_CIT0019","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1002\/eji.201646417","article-title":"Modulating sphingosine 1-phosphate signaling with DOP or FTY720 alleviates vascular and immune defects in mouse sepsis","volume":"46","author":"Hemdan","year":"2016","journal-title":"Eur J Immunol."},{"key":"2020010604480006500_CIT0020","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1021\/jm900278w","article-title":"Inhibition of sphingosine-1-phosphate lyase for the treatment of autoimmune disorders","volume":"52","author":"Bagdanoff","year":"2009","journal-title":"J Med Chem."},{"key":"2020010604480006500_CIT0021","doi-asserted-by":"crossref","first-page":"e59630","DOI":"10.1371\/journal.pone.0059630","article-title":"Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis","volume":"8","author":"Billich","year":"2013","journal-title":"PLoS One."},{"key":"2020010604480006500_CIT0022","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1021\/jm500338n","article-title":"Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis","volume":"57","author":"Weiler","year":"2014","journal-title":"J Med Chem."},{"key":"2020010604480006500_CIT0023","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1172\/JCI74188","article-title":"Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs","volume":"124","author":"Degagn\u00e9","year":"2014","journal-title":"J Clin Invest."},{"key":"2020010604480006500_CIT0024","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.4049\/jimmunol.180.4.2573","article-title":"A CD8+\/CD103HIGH T cell subset regulates TNF-mediated chronic murine ileitis","volume":"180","author":"Ho","year":"2008","journal-title":"J Immunol."},{"key":"2020010604480006500_CIT0025","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1074-7613(00)80038-2","article-title":"Impaired on\/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies","volume":"10","author":"Kontoyiannis","year":"1999","journal-title":"Immunity."},{"key":"2020010604480006500_CIT0026","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1053\/gast.2001.29568","article-title":"Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1\/Yit adoptive transfer model of Crohn\u2019s disease in mice","volume":"121","author":"Burns","year":"2001","journal-title":"Gastroenterology."},{"key":"2020010604480006500_CIT0027","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1053\/j.gastro.2004.11.053","article-title":"Proinflammatory effects of TH2 cytokines in a murine model of chronic small intestinal inflammation","volume":"128","author":"Bamias","year":"2005","journal-title":"Gastroenterology."},{"key":"2020010604480006500_CIT0028","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/cbic.200800809","article-title":"Synthesis of a fluorogenic analogue of sphingosine-1-phosphate and its use to determine sphingosine-1-phosphate lyase activity","volume":"10","author":"Bedia","year":"2009","journal-title":"Chembiochem."},{"key":"2020010604480006500_CIT0029","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1194\/jlr.M009449","article-title":"Lipidomics reveals a remarkable diversity of lipids in human plasma","volume":"51","author":"Quehenberger","year":"2010","journal-title":"J Lipid Res."},{"key":"2020010604480006500_CIT0030","doi-asserted-by":"crossref","first-page":"e1005112","DOI":"10.1371\/journal.pcbi.1005112","article-title":"Cytofkit: a bioconductor package for an integrated mass cytometry data analysis pipeline","volume":"12","author":"Chen","year":"2016","journal-title":"PLoS Comput Biol."},{"key":"2020010604480006500_CIT0031","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.chembiol.2016.04.007","article-title":"Component of caramel food coloring, THI, causes lymphopenia indirectly via a key metabolic intermediate","volume":"23","author":"Ohtoyo","year":"2016","journal-title":"Cell Chem Biol."},{"key":"2020010604480006500_CIT0032","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.4049\/jimmunol.175.5.2913","article-title":"Sphingosine 1-phosphate receptors regulate chemokine-driven transendothelial migration of lymph node but not splenic T cells","volume":"175","author":"Yopp","year":"2005","journal-title":"J Immunol."},{"key":"2020010604480006500_CIT0033","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cellsig.2004.08.006","article-title":"In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1-phosphate: mechanistic insights","volume":"17","author":"McVerry","year":"2005","journal-title":"Cell Signal."},{"key":"2020010604480006500_CIT0034","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1164\/rccm.200405-684OC","article-title":"Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury","volume":"170","author":"McVerry","year":"2004","journal-title":"Am J Respir Crit Care Med."},{"key":"2020010604480006500_CIT0035","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/ni1269","article-title":"Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses","volume":"6","author":"Wei","year":"2005","journal-title":"Nat Immunol."},{"key":"2020010604480006500_CIT0036","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jcb.240580208","article-title":"Ceramide: a stress signal and mediator of growth suppression and apoptosis","volume":"58","author":"Obeid","year":"1995","journal-title":"J Cell Biochem."},{"key":"2020010604480006500_CIT0037","doi-asserted-by":"crossref","first-page":"15396","DOI":"10.1074\/jbc.M314291200","article-title":"Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration","volume":"279","author":"Allende","year":"2004","journal-title":"J Biol Chem."},{"key":"2020010604480006500_CIT0038","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.autrev.2017.03.007","article-title":"Modulation of sphingosine-1-phosphate in inflammatory bowel disease","volume":"16","author":"Peyrin-Biroulet","year":"2017","journal-title":"Autoimmun Rev."},{"key":"2020010604480006500_CIT0039","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nrd4099","article-title":"Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond","volume":"12","author":"Kunkel","year":"2013","journal-title":"Nat Rev Drug Discov."},{"key":"2020010604480006500_CIT0040","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/mi.2016.35","article-title":"Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease","volume":"10","author":"Karuppuchamy","year":"2017","journal-title":"Mucosal Immunol."},{"key":"2020010604480006500_CIT0041","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1189\/jlb.3HI0614-303R","article-title":"Chemokine receptor CCR7 regulates the intestinal TH1\/TH17\/treg balance during Crohn\u2019s-like murine ileitis","volume":"97","author":"McNamee","year":"2015","journal-title":"J Leukoc Biol."},{"key":"2020010604480006500_CIT0042","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1136\/gutjnl-2011-301272","article-title":"Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis","volume":"62","author":"McNamee","year":"2013","journal-title":"Gut."},{"key":"2020010604480006500_CIT0043","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1053\/j.gastro.2008.02.085","article-title":"Role of beta7 integrin and the chemokine\/chemokine receptor pair CCL25\/CCR9 in modeled TNF-dependent Crohn\u2019s disease","volume":"134","author":"Apostolaki","year":"2008","journal-title":"Gastroenterology."},{"key":"2020010604480006500_CIT0044","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.4049\/jimmunol.174.4.2343","article-title":"L-selectin, alpha 4 beta 1, and alpha 4 beta 7 integrins participate in CD4+ T cell recruitment to chronically inflamed small intestine","volume":"174","author":"Rivera-Nieves","year":"2005","journal-title":"J Immunol."},{"key":"2020010604480006500_CIT0045","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.immuni.2009.08.012","article-title":"Intestinal effector T cells in health and disease","volume":"31","author":"Maynard","year":"2009","journal-title":"Immunity."},{"key":"2020010604480006500_CIT0046","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.1198704","article-title":"Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum","volume":"332","author":"Bendall","year":"2011","journal-title":"Science."},{"key":"2020010604480006500_CIT0047","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.trim.2006.02.004","article-title":"Evidence that FTY720 induces rat thymocyte apoptosis","volume":"15","author":"Isoyama","year":"2006","journal-title":"Transpl Immunol."},{"key":"2020010604480006500_CIT0048","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cbpb.2012.05.006","article-title":"The control of the balance between ceramide and sphingosine-1-phosphate by sphingosine kinase: oxidative stress and the seesaw of cell survival and death","volume":"163","author":"Van Brocklyn","year":"2012","journal-title":"Comp Biochem Physiol B Biochem Mol Biol."},{"key":"2020010604480006500_CIT0049","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.trim.2010.06.003","article-title":"FTY720 mediates cytochrome c release from mitochondria during rat thymocyte apoptosis","volume":"23","author":"Matsumura","year":"2010","journal-title":"Transpl Immunol."},{"key":"2020010604480006500_CIT0050","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/intimm\/dxt069","article-title":"S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1","volume":"26","author":"Maeda","year":"2014","journal-title":"Int Immunol."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ibdjournal\/article-pdf\/26\/2\/216\/31717788\/izz174.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ibdjournal\/article-pdf\/26\/2\/216\/31717788\/izz174.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T04:48:17Z","timestamp":1578286097000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/2\/216\/5550850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,6]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,12,6]]},"published-print":{"date-parts":[[2020,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izz174","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,2]]},"published":{"date-parts":[[2019,12,6]]}}}