FOXO1, T-Cell Trafficking and Immune Responses

  • Florent Carrette
  • Stéphanie Fabre
  • Georges Bismuth
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 665)

Abstract

Efficient T-cell adaptive immune response require a faultless coordination between migration of naive T-cells into secondary lymphoid organs and critical biological outcomes driven by antigen such as cell division and cell differentiation into effector and memory cells. Recent works have shown that the phosphoinositide 3-kinase (PI3K) pathway could govern several of these processes. In this control, transcriptional factors of the Forkhead box O (FoxO) family, in particular FOXO1, a downstream effector ofPI3K, appears to play a major role by coordinating both cellular proliferation of T-cells after antigen recognition and expression of homing molecules essential for their trafficking in the body.

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References

  1. 1.
    Lasky LA, Singer MS, Yednock TA et al. Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell 1989; 56:1045–1055.CrossRefPubMedGoogle Scholar
  2. 2.
    Spertini O, Luscinskas FW, Kansas GS et al. Leukocyte adhesion molecule-l (LAM-I, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. J Immunol 1991; 147:2565–2573.PubMedGoogle Scholar
  3. 3.
    Tedder TF, Isaacs CM, Ernst TJ et al. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule,LAM-I. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins. J Exp Med 1989; 170:123–133.CrossRefPubMedGoogle Scholar
  4. 4.
    Arbones ML, Ord DC, Ley K et al. Lymphocyte homing and leukocyte rolling and migration are impaired in Lselectin-deficient mice. Immunity 1994; 1:247–260.CrossRefPubMedGoogle Scholar
  5. 5.
    Jung TM, Gallatin WM, Weissman IL et al. Down-regulation of homing receptors after T-cell activation. J Immunol 1988; 141:4110–4117.PubMedGoogle Scholar
  6. 6.
    Harris NL, Watt V, Ronchese F et at. Differential T-cell function and fate in lymph node and nonlymphoid tissues. J Exp Med 2002; 195:317–326.CrossRefPubMedGoogle Scholar
  7. 7.
    Faveeuw C, Preece G, Ager A. Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases. Blood 2001; 98:688–695.CrossRefPubMedGoogle Scholar
  8. 8.
    Preece G, Murphy G, Ager A. Metalloproteinase-mediated regulation of L-selectin levels on leucocytes. J Biol Chem 1996; 271:11634–11640.CrossRefPubMedGoogle Scholar
  9. 9.
    Peschon JJ, Slack JL, Reddy P et al. An essential role for ectodomain shedding in mammalian development. Science 1998; 282:1281–1284.CrossRefPubMedGoogle Scholar
  10. 10.
    Galkina E, Tanousis K, Preece G et al. L-selectin shedding does not regulate constitutive T-cell trafficking but controls the migration pathways of antigen-activated T-lymphocytes. J Exp Med 2003; 198:1323–1335.CrossRefPubMedGoogle Scholar
  11. 11.
    Venturi GM, Tu L, Kadono T et al. Leukocyte migration is regulated by L-selectin endoproteolytic release. Immunity 2003; 19:713–724.CrossRefPubMedGoogle Scholar
  12. 12.
    Chao CC, Jensen R, Dailey MO. Mechanisms of L-selectin regulation by activated T-cells. J Immunol 1997; 159:1686–1694.PubMedGoogle Scholar
  13. 13.
    Cyster JG. Chemokines and cell migration in secondary lymphoid organs. Science 1999; 286:2098–2102.CrossRefPubMedGoogle Scholar
  14. 14.
    Campbell JJ, Bowman EP, Murphy K et al. 6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7. J Cell Biol 1998; 141:1053–1059.CrossRefPubMedGoogle Scholar
  15. 15.
    Yoshida R, Nagira M, Kitaura M et al. Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7. J Biol Chem 1998; 273:7118–7122.CrossRefPubMedGoogle Scholar
  16. 16.
    Nakano H, Tamura T, Yoshimoto T et al. Genetic defect in T-lymphocyte-specific homing into peripheral lymph nodes. Eur J Immunol 1997; 27:215–221.CrossRefPubMedGoogle Scholar
  17. 17.
    Gunn MD, Kyuwa S, Tam C et al. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med 1999; 189:451–460.CrossRefPubMedGoogle Scholar
  18. 18.
    Luther SA, Tang HL, Hyman PL et al. Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. Proc Natl Acad Sci USA 2000; 97:12694–12699.CrossRefPubMedGoogle Scholar
  19. 19.
    Stein JV, Rot A, Luo Y et al. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T-lymphocytes in peripheral lymph node high endothelial venules. J Exp Med 2000; 191:61–76.CrossRefPubMedGoogle Scholar
  20. 20.
    Warnock RA, Campbell JJ, Dorf ME et al. The role of chemokines in the microenvironmental control of T versus B-cell arrest in Peyer’s patch high endothelial venules. J Exp Med 2000; 191:77–88.CrossRefPubMedGoogle Scholar
  21. 21.
    Forster R, Schubel A, Breitfeld D et al. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999; 99:23–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Campbell JJ, Hedrick J, Zlotnik A et al. Chemokines and the arrest of lymphocytes rolling under How conditions. Science 1998;279:381–384.CrossRefPubMedGoogle Scholar
  23. 23.
    Constantin G, Majeed M, Giagulli C et al. Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under How. Immunity 2000; 13:759–769.CrossRefPubMedGoogle Scholar
  24. 24.
    Tangemann K, Gunn MD, Giblin P et al. A high endothelial cell-derived chemokine induces rapid, efficient and subset-selective arrest of rolling T-lymphocytes on a reconstituted endothelial substrate. J Immunol 1998; 161:6330–6337.PubMedGoogle Scholar
  25. 25.
    Gunn MD, Tangemann K, Tam C et al. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T-lymphocytes. Proc Natl Acad Sci USA 1998; 95:258–263.CrossRefPubMedGoogle Scholar
  26. 26.
    Nagira M, Imai T, Yoshida R et al. A lymphocyte-specific CC chemokine, secondary lymphoid tissue chemokine (SLC), is a highly efficient chemoattractant for B-cells and activated T-cells. Eur J Immunol 1998; 28:1516–1523.CrossRefPubMedGoogle Scholar
  27. 27.
    Baekkevold ES, Yamanaka T, Palframan RT et al. The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T-cell recruitment. J Exp Med 2001; 193:1105–1112.CrossRefPubMedGoogle Scholar
  28. 28.
    Bemfield M, Gotte M, Park PW et al. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 1999; 68:729–777.CrossRefGoogle Scholar
  29. 29.
    Miyasaka M, Tanaka T. Lymphocyte trafficking across high endothelial venules: dogmas and enigmas. Nat Rev Immunol 2004; 4:360–370.CrossRefPubMedGoogle Scholar
  30. 30.
    Seminario MC, Precht P, Wersto RP et al. PTEN expression in PTEN-null leukaemic T-cell lines leads to reduced proliferation via slowed cell cycle progression. Oncogene 2003; 22:8195–8204.CrossRefPubMedGoogle Scholar
  31. 31.
    Fabre S, Carrette F, Chen J et al. FOX01 regulates L-Selectin and a network of human T-cell homing molecules downstream of phosphatidylinositol 3-kinase. J Immunol 2008; 181:2980–2989.PubMedGoogle Scholar
  32. 32.
    Sinclair LV, Finlay D, Feijoo C et al. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T-lymphocyte trafficking. Nat Immunol 2008; 9:513–521.CrossRefPubMedGoogle Scholar
  33. 33.
    Paik JH, Kollipara R, Chu G et al. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 2007; 128:309–323.CrossRefPubMedGoogle Scholar
  34. 34.
    Dengler HS, Baracho GY, Omori SA et al. Distinct functions for the transcription factor Foxo1 at various stages of B-cell differentiation. Nat Immunol 2008Google Scholar
  35. 35.
    Chen J, Yusuf I, Andersen HM et al. FOXO transcription factors cooperate with delta EF1 to activate growth suppressive genes in B-lymphocytes. J Immunol 2006; 176:2711–2721.PubMedGoogle Scholar
  36. 36.
    Calnan DR, Brunet A. The FoxO code. Oncogene 2008; 27:2276–2288.CrossRefPubMedGoogle Scholar
  37. 37.
    Bajenoff M, Egen JG, Koo LY et al. Stromal cell networks regulate lymphocyte entry, migration and territoriality in lymph nodes. Immunity 2006; 25:989–1001.CrossRefPubMedGoogle Scholar
  38. 38.
    Bousso P, Robey E. Dynamics of CD8+ T-cell priming by dendritic cells in intact lymph nodes. Nat Immunol 2003; 4:579–585.CrossRefPubMedGoogle Scholar
  39. 39.
    Mempel TR, Henrickson SE, Von Andrian UH. T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 2004; 427:154–159.CrossRefPubMedGoogle Scholar
  40. 40.
    Miller MJ, Safrina O, Parker I et al. Imaging the single cell dynamics of CD4+ T-cell activation by dendritic cells in lymph nodes. J Exp Med 2004; 200:847–856.CrossRefPubMedGoogle Scholar
  41. 41.
    Miller MJ, Wei SH, Cahalan MD et al. Autonomous T-cell trafficking examined in vivo with intravital two-photon microscopy. Proc Natl Acad Sci USA 2003; 100:2604–2609.CrossRefPubMedGoogle Scholar
  42. 42.
    Miller MJ, Wei SH, Parker I et al. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 2002; 296:1869–1873.CrossRefPubMedGoogle Scholar
  43. 43.
    Miller MJ, Hejazi AS, Wei SH et al. T-cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T-cell motility in the lymph node. Proc Natl Acad Sci USA 2004; 101:998–1003.CrossRefPubMedGoogle Scholar
  44. 44.
    Asperti-Boursin F, Real E, Bismuth G et al. CCR7 ligands control basal T-cell motility within lymph node slices in a phosphoinositide 3-kinase-independent manner. J Exp Med 2007; 204:1167–1179.CrossRefPubMedGoogle Scholar
  45. 45.
    Okada T, Cyster JG. CC chemokine receptor 7 contributes to Gi-dependent T-cell motility in the lymph node. J Immunol 2007; 178:2973–2978.PubMedGoogle Scholar
  46. 46.
    Worbs T, Mempel TR, Bolter J et al. CCR7 ligands stimulate the intranodal motility of T-lymphocytes in vivo. J Exp Med 2007; 204:489–495.CrossRefPubMedGoogle Scholar
  47. 47.
    Stoll S, Delon J, Brotz TM et al. Dynamic imaging of T-cell-dendritic cell interactions in lymph nodes. Science 2002; 296:1873–1876.CrossRefPubMedGoogle Scholar
  48. 48.
    Birkenkamp KU, Coffer PJ. FOXO transcription factors as regulators of immune homeostasis: molecules to die for? I Immunol 2003; 171:1623–1629.bl]ReferencesGoogle Scholar
  49. 49.
    Biggs WH 3rd, Meisenhelder J, Hunter T et al. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA 1999; 96:7421–7426.CrossRefPubMedGoogle Scholar
  50. 50.
    Rena G, Guo S, Cichy SC et al. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem 1999; 274:17179–17183.CrossRefPubMedGoogle Scholar
  51. 51.
    Zhang X, Gan L, Pan H et al. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. J Biol Chem 2002; 277:45276–45284.CrossRefPubMedGoogle Scholar
  52. 52.
    Brunet A, Bonni A, Zigmond MJ et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96:857–868.CrossRefPubMedGoogle Scholar
  53. 53.
    Medema RH, Kops GJ, Bos JL et al. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 2000; 404:782–787.CrossRefPubMedGoogle Scholar
  54. 54.
    Stahl M, Dijkers PF, Kops GJ et al. The forkhead transcription factor FoxO regulates transcription of p27Kipl and Bim in response to IL-2. J Immunol 2002; 168:5024–5031.PubMedGoogle Scholar
  55. 55.
    Harriague J, Bismuth G. Imaging antigen-induced PI3K activation in T-cells. Nat Immunol 2002; 3:1090–1096.CrossRefPubMedGoogle Scholar
  56. 56.
    Fabre S, Lang V, Harriague J et al. Stable activation of phosphatidylinositol 3-kinase in the T-cell immunological synapse stimulates Akt signaling to FoxO1 nuclear exclusion and cell growth control. J Immunol 2005; 174:4161–4171.PubMedGoogle Scholar
  57. 57.
    Yusuf I, Zhu X, Kharas MG et al. Optimal B-cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors. Blood 2004; 104:784–787.CrossRefPubMedGoogle Scholar
  58. 58.
    Charvet C, Canonigo AJ, Becart S et al. Vav1 promotes T-cell cycle progression by linking TCR/CD28 costimulation to FOXO1 and p27kip 1 expression. J Immunol 2006; 177:5024–5031.PubMedGoogle Scholar
  59. 59.
    Ramaswamy S, Nakamura N, Sansal I et al. A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell 2002; 2:81–91.CrossRefPubMedGoogle Scholar
  60. 60.
    Okkenhaug K, Bilancio A, Farjot G et al. Impaired B-and T-cell antigen receptor signaling in pll0delta PI 3-kinase mutant mice. Science 2002; 297:1031–1034.PubMedGoogle Scholar
  61. 61.
    Okkenhaug K, Patton DT, Bilancio A et al. The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol 2006; 177:5122–5128.PubMedGoogle Scholar
  62. 62.
    Yusuf I, Fruman DA. Regulation of quiescence in lymphocytes. Trends Immunol 2003; 24:380–386.CrossRefPubMedGoogle Scholar
  63. 63.
    Brunet A, Sweeney LB, Sturgill JF et al. Stress-dependent regulation of FOXO transcription factors by the SIRT 1 deacetylase. Science 2004; 303:2011–2015.CrossRefPubMedGoogle Scholar
  64. 64.
    Essers MA, de Vries-Smits LM, Barker N et al. Functional interaction between beta-eatenin and FOXO in oxidative stress signaling. Science 2005; 308:1181–1184.CrossRefPubMedGoogle Scholar
  65. 65.
    Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 2005; 24:7410–7425.CrossRefPubMedGoogle Scholar
  66. 66.
    Seoane J, Le HV, Shen L et al. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 2004; 117:211–223.CrossRefPubMedGoogle Scholar
  67. 67.
    Lin L, Hron JD, Peng SL. Regulation of NF-kappaB, Th activation and autoinflammation by the forkhead transcription factor Foxo3a. Immunity 2004; 21:203–213.CrossRefPubMedGoogle Scholar
  68. 68.
    You H, Pellegrini M, Tsuchihara K et al. FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal. J Exp Med 2006; 203:1657–1663.CrossRefPubMedGoogle Scholar
  69. 69.
    Forsdyke DR. cDNA cloning of mRNAS which increase rapidly in human lymphocytes cultured with concanavalin-A and cycloheximide. Biochem Biophys Res Commun 1985; 129:619–625.CrossRefPubMedGoogle Scholar
  70. 70.
    Virolle T, Krones-Herzig A, Baron V et al. Egr1 promotes growth and survival of prostate cancer cells. Identification of novel Egr1 target genes. J Biol Chem 2003; 278:11802–11810.CrossRefPubMedGoogle Scholar
  71. 71.
    Yan YX, Nakagawa H, Lee MH et al. Transforming growth factor-alpha enhances cyclin D1 transcription through the binding of early growth response protein to a cis-regulatory element in the cyclin D1 promoter. J Biol Chem 1997; 272:33181–33190.CrossRefPubMedGoogle Scholar
  72. 72.
    Center DM, Cruikshank WW, Zhang Y. Nuclear pro-IL-16 regulation of T-cell proliferation: p27(KIP1)-dependent G0/G1 arrest mediated by inhibition of Skp2 transcription. J Immunol 2004; 172:1654–1660.PubMedGoogle Scholar
  73. 73.
    Mari B, Guerin S, Maulon L et al. Endopeptidase 24.11 (CD10/NEP) is required for phorbol ester-induced growth arrest in Jurkat T-cells. FASEBJ 1997; 11:869–879.Google Scholar
  74. 74.
    Rowan W, Tite J, Topley P et al. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B-and T-lymphoma cell lines and subsequent emergence of CD52-deficient cells. Immunology 1998; 95:427–436.CrossRefPubMedGoogle Scholar
  75. 75.
    Cutrona G, Leanza N, Ulivi M et al. Expression of CD10 by human T-cells that undergo apoptosis both in vitro and in vivo. Blood 1999; 94:3067–3076.PubMedGoogle Scholar
  76. 76.
    Sumitomo M, Iwase A, Zheng R et al. Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN. Cancer Cell 2004; 5:67–78.CrossRefPubMedGoogle Scholar
  77. 77.
    Cyster JG. Chemokines, sphingosine-1-phosphate and cell migration in secondary lymphoid organs. Annu Rev Immunol 2005; 23:127–159.CrossRefPubMedGoogle Scholar
  78. 78.
    Sallusto F, Kremmer E, Palermo B et al. Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T-cells. Eur J Immunol 1999; 29:2037–2045.CrossRefPubMedGoogle Scholar
  79. 79.
    Sallusto F, Lenig D, Forster R et al. Two subsets of memory T-lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401:708–712.CrossRefPubMedGoogle Scholar
  80. 80.
    Weninger W, Crowley MA, Manjunath N et al. Migratory properties of naive, effector and memory CD8(+) T-cells. J Exp Med 2001; 194:953–966.CrossRefPubMedGoogle Scholar
  81. 81.
    Bajenoff M, Guerder S. Homing to nonlymphoid tissues is not necessary for effector Th1 cell differentiation. J Immunol 2003; 171:6355–6362.PubMedGoogle Scholar
  82. 82.
    Riou C, Yassine-Diab B, Van grevenynghe J et al. Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T-cells. J Exp Med 2007; 204:79–91.CrossRefPubMedGoogle Scholar
  83. 83.
    Fukuoka M, Daitoku H, Hatta M et al. Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation. Int J Mol Med 2003; 12:503–508.PubMedGoogle Scholar
  84. 84.
    Motta MC, Divecha N, Lemieux M et al. Mammalian SIRT1 represses forkhead transcription factors. Cell 2004; 116:551–563.CrossRefPubMedGoogle Scholar
  85. 85.
    Puigserver P, Rhee J, Donovan J et al. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 2003; 423:550–555.CrossRefPubMedGoogle Scholar
  86. 86.
    van der Horst A, Tertoolen LG, de Vries-Smits LM et al. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem 2004; 279:28873–28879.CrossRefPubMedGoogle Scholar
  87. 87.
    Suzuki S, Enosawa S, Kakefuda T et al. A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation. Transplantation 1996; 61:200–205.CrossRefPubMedGoogle Scholar
  88. 88.
    Chiba K, Yanagawa Y, Masubuchi Y et al. FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number ofcirculating mature lymphocytes by acceleration of lymphocyte homing. J Immunol 1998; 160:5037–5044.PubMedGoogle Scholar
  89. 89.
    Mandala S, Hajdu R, Bergstrom J et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002; 296:346–349.CrossRefPubMedGoogle Scholar
  90. 90.
    Kuo CT, Veselits ML, Leiden JM. LKLF: A transcriptional regulator of single-positive T-cell quiescence and survival. Science 1997; 277:1986–1990.CrossRefPubMedGoogle Scholar
  91. 91.
    Carlson CM, Endrizzi BT, Wu J et al. Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 2006; 442:299–302.CrossRefPubMedGoogle Scholar
  92. 92.
    Sebzda E, Zou Z, Lee JS et al. Transcription factor KLF2 regulates the migration of naive T-cells by restricting chemokine receptor expression patterns. Nat Immunol 2008; 9:292–300.CrossRefPubMedGoogle Scholar
  93. 93.
    Bai A, Hu H, Yeung M et al. Kruppel-like factor 2 controls T-cell trafficking by activating L-selectin (CD62L) and sphingosine-1-phosphate receptor 1 transcription. J Immunol 2007; 178:7632–7639.PubMedGoogle Scholar
  94. 94.
    Haaland RE, Yu W, Rice AP. Identification of LKLF-regulated genes in quiescent CD4+ T-lymphocytes. Mol Immunol 2005; 42:627–641.CrossRefPubMedGoogle Scholar
  95. 95.
    Hatta M, Cirillo LA. Chromatin opening and stable perturbation of core histone: DNA contacts by FoxO1. J Biol Chem 2007; 282:35583–35593.CrossRefPubMedGoogle Scholar
  96. 96.
    Shiow LR, Rosen DB, Brdickova N et al. CD69 acts downstream ofinterferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 2006; 440:540–544.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer+Business Media 2009

Authors and Affiliations

  • Florent Carrette
    • 1
    • 2
  • Stéphanie Fabre
    • 1
    • 2
  • Georges Bismuth
    • 1
    • 2
  1. 1.Centre National de la Recherche Scientifique Equipe labellisée par la Ligue Nationale contre le CancerInstitut Cochin Université Paris DescartesParisFrance
  2. 2.Unité 567Institut National de la Santé et de la Recherche MédicaleParisFrance

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