Fine-Tuning Antitumor Responses Through the Control of Galectin–Glycan Interactions: An Overview

  • Mariana Salatino
  • Gabriel A. RabinovichEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 677)


In recent years, we have witnessed critical advances in genomics and proteomics which contributed to delineate the “tumor progression signature”. This includes the altered expression of genes and proteins not only in tumor cells, but also in tumor-associated stromal, endothelial, and immune cells. Adding more complexity to this bewildering information, efforts are being made to define the “glycosylation signature” of the tumor microenvironment, which results from the abnormal expression and activity of glycosyltransferases, glycosidases, and enzyme chaperons. The multiple combinatorial possibilities of glycan structures expressed by neoplastic versus normal tissue provide enormous potential for information display and expand potential therapeutic opportunities. The responsibility of deciphering the biological information encoded by the tumor-associated glycome is partially assigned, to distinct families of endogenous glycan-binding proteins or lectins, whose expression and function are regulated in cancerous tissues. Galectins, a family of evolutionarily conserved glycan-binding proteins, can control tumor progression by directly influencing tumor growth or by modulating cell migration, angiogenesis, and tumor–immune escape. In this review, we will highlight recent findings on how galectin–glycan lattices control the dialogue between tumor and immune cells and how these interactions could be exploited for therapeutic purposes.

Key words

Glycosylation Cancer Tumor microenvironment Tumor immunity Galectins 



We apologize to the many authors whose papers could not be cited owing to space limitations. We are grateful to D. Croci for helping in the design of figure. Work in authors’ laboratory is supported by grants from The Cancer Research Institute “Elaine R. Shephard” Award (USA), The Prostate Cancer Foundation (UK), Fundación Sales (Argentina), and Agencia Nacional de Promoción Científica y Tecnológica (FONCYT, PICT 2006-603; PICT 2007-903).


  1. 1.
    Ohtsubo K and Marth JD. (2006) Glycosylation in cellular mechanisms of health and disease. Cell 126: 855–867.PubMedCrossRefGoogle Scholar
  2. 2.
    van Kooyk Y and Rabinovich GA. (2008) Protein–glycan interactions in the control of innate and adaptive immune responses. Nat Immunol 9: 593–601.PubMedCrossRefGoogle Scholar
  3. 3.
    Rabinovich GA and Toscano MA. (2009) Turning ‘sweet’ on immunity: galectin–glycan interactions in immune tolerance and inflammation. Nat Rev Immunol 9: 338–352.PubMedCrossRefGoogle Scholar
  4. 4.
    Hakomori S. (2002) Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA 99: 10231–10233.PubMedCrossRefGoogle Scholar
  5. 5.
    Lau KS and Dennis JW. (2008) N-Glycans in cancer progression. Glycobiology 18: 750–760.PubMedCrossRefGoogle Scholar
  6. 6.
    Kim YJ and Varki A. (1997) Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconj J 14: 569–576.PubMedCrossRefGoogle Scholar
  7. 7.
    Dube DH and Bertozzi CR. (2003) Metabolic oligosaccharide engineering as a tool for glycobiology. Curr Opin Chem Biol 7: 616–625.PubMedCrossRefGoogle Scholar
  8. 8.
    Dube DH and Bertozzi CR. (2005) Glycans in cancer and inflammation – potential for therapeutics and diagnostics. Nat Rev Drug Discov 4: 477–488.PubMedCrossRefGoogle Scholar
  9. 9.
    Keppler OT, Horstkorte R, Pawlita M, et al. (2001) Biochemical engineering of the N-acyl side chain of sialic acid: biological implications. Glycobiology 11: 11R–18R.PubMedCrossRefGoogle Scholar
  10. 10.
    Prescher JA, Dube DH and Bertozzi CR. (2004) Chemical remodelling of cell surfaces in living animals. Nature 430: 873–877.PubMedCrossRefGoogle Scholar
  11. 11.
    Hollingsworth MA and Swanson BJ. (2004) Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4: 45–60.PubMedCrossRefGoogle Scholar
  12. 12.
    Hakomori S. (2000) Traveling for the glycosphingolipid path. Glycoconj J 17: 627–647.PubMedCrossRefGoogle Scholar
  13. 13.
    Rabinovich GA, Toscano MA, Jackson SS, et al. (2007) Functions of cell surface galectin-glycoprotein lattices. Curr Opin Struct Biol 17: 513–520.PubMedCrossRefGoogle Scholar
  14. 14.
    Yang RY, Rabinovich GA and Liu FT. (2008) Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 10: e17.PubMedCrossRefGoogle Scholar
  15. 15.
    Rabinovich GA and Ilarregui JM. (2009) Conveying glycan information into T-cell homeostatic programs: a challenging role for galectin-1 in inflammatory and tumor microenvironments. Immunol Rev 230: 144–159.PubMedCrossRefGoogle Scholar
  16. 16.
    Brewer CF, Miceli MC and Baum LG. (2002) Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions. Curr Opin Struct Biol 12: 616–623.PubMedCrossRefGoogle Scholar
  17. 17.
    Laderach DJ, Compagno D, Toscano MA, et al. (2010) Dissecting the signal transduction pathways triggered by galectin–glycan interactions in physiological and pathological settings. IUBMB Life 62(1):1–13.PubMedGoogle Scholar
  18. 18.
    Kubach J, Lutter P, Bopp T, et al. (2007) Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood 110:1550–1558.PubMedCrossRefGoogle Scholar
  19. 19.
    Hirabayashi J, Hashidate T, Arata Y, et al. (2002) Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochim Biophys Acta 1572: 232–254.PubMedCrossRefGoogle Scholar
  20. 20.
    Stowell SR, Arthur CM, Mehta P, et al. (2008) Galectin-1, -2, and -3 exhibit differential recognition of sialylated glycans and blood group antigens. J Biol Chem 283: 10109–10123.PubMedCrossRefGoogle Scholar
  21. 21.
    Liu FT and Rabinovich GA. (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5: 29–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Salatino M, Croci DO, Bianco GA, et al. (2008) Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer. Expert Opin Biol Ther 8: 45–57.PubMedCrossRefGoogle Scholar
  23. 23.
    Elola MT, Wolfenstein-Todel C, Troncoso MF, et al. (2007) Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cell Mol Life Sci 64: 1679–1700.PubMedCrossRefGoogle Scholar
  24. 24.
    Perillo NL, Pace KE, Seilhamer JJ, et al. (1995) Apoptosis of T cells mediated by galectin-1. Nature 378: 736–739.PubMedCrossRefGoogle Scholar
  25. 25.
    Thijssen VL, Postel R, Brandwijk RJ, et al. (2006) Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci U S A 103: 15975–15980.PubMedCrossRefGoogle Scholar
  26. 26.
    Le Mercier M, Fortin S, Mathieu V, et al. (2009) Galectin 1 proangiogenic and promigratory effects in the Hs683 oligodendroglioma model are partly mediated through the control of BEX2 expression. Neoplasia 11: 485–496.PubMedGoogle Scholar
  27. 27.
    Rubinstein N, Alvarez M, Zwirner NW, et al. (2004) Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; a potential mechanism of tumor-immune privilege. Cancer Cell 5: 241–251.PubMedCrossRefGoogle Scholar
  28. 28.
    Juszczynski P, Ouyang J, Monti S, et al. (2007) The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A 104: 13134–13139.PubMedCrossRefGoogle Scholar
  29. 29.
    Gandhi MK, Moll G, Smith C, et al. (2007) Galectin-1 mediated suppression of Epstein–Barr virus specific T-cell immunity in classic Hodgkin lymphoma. Blood 110: 1326–1329.PubMedCrossRefGoogle Scholar
  30. 30.
    Valenzuela HF, Pace KE, Cabrera PV, et al. (2007) O-glycosylation regulates LNCaP prostate cancer cell susceptibility to apoptosis induced by galectin-1. Cancer Res 67: 6155–6162.PubMedCrossRefGoogle Scholar
  31. 31.
    Le QT, Shi G, Cao H, et al. (2005) Galectin-1: a link between tumor hypoxia and tumor immune privilege. J Clin Oncol 23: 8932–8941.PubMedCrossRefGoogle Scholar
  32. 32.
    Peng W, Wang HY, Miyahara Y, et al. (2008) Tumor-associated galectin-3 modulates the function of tumor-reactive T cells. Cancer Res 68: 7228–7236.PubMedCrossRefGoogle Scholar
  33. 33.
    Zubieta MR, Furman D, Barrio M, et al. (2006) Galectin-3 expression correlates with apoptosis of tumor-associated lymphocytes in human melanoma biopsies. Am J Pathol 168: 1666–1675.PubMedCrossRefGoogle Scholar
  34. 34.
    Klibi J, Niki T, Riedel A, et al. (2009) Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein–Barr virus-infected nasopharyngeal carcinoma cells. Blood 113: 1957–1966.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhu C, Anderson AC, Schubart A, et al. (2005) The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 6: 1245–1252.PubMedCrossRefGoogle Scholar
  36. 36.
    Nagahara K, Arikawa T, Oomizu S, et al. (2008) Galectin-9 increases Tim-3+ dendritic cells and CD8+ T cells and enhances antitumor immunity via galectin-9-Tim-3 interactions. J Immunol 181: 7660–7669.PubMedGoogle Scholar
  37. 37.
    Allione A, Wells V, Forni G, et al. (1998) Beta-galactoside-binding protein (beta GBP) alters the cell cycle, up-regulates expression of the alpha- and beta-chains of the IFN-gamma receptor, and triggers IFN-gamma-mediated apoptosis of activated human T lymphocytes. J Immunol 161: 2114–2119.PubMedGoogle Scholar
  38. 38.
    Hahn HP, Pang M, He J, et al. (2004) Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death. Cell Death Differ 11: 1277–1286.PubMedCrossRefGoogle Scholar
  39. 39.
    Brandt B, Buchse T, Abou-Eladab EF, et al. (2008) Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes. Histochem Cell Biol 129: 599–609.PubMedCrossRefGoogle Scholar
  40. 40.
    Matarrese P, Tinari A, Mormone E, et al. (2005) Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission. J Biol Chem 280: 6969–6985.PubMedCrossRefGoogle Scholar
  41. 41.
    Vespa GN, Lewis LA, Kozak KR, et al. (1999) Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation. J Immunol 162: 799–806.PubMedGoogle Scholar
  42. 42.
    Rabinovich GA, Alonso CR, Sotomayor CE, et al. (2000) Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of the AP-1 transcription factor and downregulation of Bcl-2. Cell Death Differ 7: 747–753.PubMedCrossRefGoogle Scholar
  43. 43.
    Stowell SR, Karmakar S, Arthur CM, et al. (2009) Galectin-1 induces reversible phosphatidylserine exposure at plasma membrane. Mol Biol Cell 20: 1408–1418.PubMedCrossRefGoogle Scholar
  44. 44.
    Pang M, He J, Johnson P, et al. (2009) CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells. J Immunol 182: 7001–7008.PubMedCrossRefGoogle Scholar
  45. 45.
    Toscano MA, Bianco GA, Ilarregui JM, et al. (2007) Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8: 825–834.PubMedCrossRefGoogle Scholar
  46. 46.
    Earl LA, Bi S and Baum LG. (2010) N- and O-glycans modulate galectin-1 binding, CD45 signaling and T cell death. J Biol Chem 285: 2232–2244.PubMedCrossRefGoogle Scholar
  47. 47.
    Galvan M, Tsuboi S, Fukuda M, et al. (2000) Expression of a specific glycosyltransferase enzyme regulates T cell death mediated by galectin-1. J Biol Chem 275: 16730–16737.PubMedCrossRefGoogle Scholar
  48. 48.
    Amano M, Galvan M, He J, et al. (2003) The ST6Gal I sialyltransferase selectively modifies N-glycans on CD45 to negatively regulate galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death. J Biol Chem 278: 7469–7475.PubMedCrossRefGoogle Scholar
  49. 49.
    Pace KE, Lee C, Stewart PL, et al. (1999) Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1. J Immunol 163: 3801–3811.PubMedGoogle Scholar
  50. 50.
    Sturm A, Lensch M, Andre S, et al. (2004) Human galectin-2: novel inducer of T cell apoptosis with distinct profile of caspase activation. J Immunol 173: 3825–3837.PubMedGoogle Scholar
  51. 51.
    Bi S, Earl LA, Jacobs L, et al. (2008) Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. J Biol Chem 283: 12248–12258.PubMedCrossRefGoogle Scholar
  52. 52.
    Kashio Y, Nakamura K, Abedin MJ, et al. (2003) Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway. J Immunol 170: 3631–3636.PubMedGoogle Scholar
  53. 53.
    Hsu DK, Yang RY, Pan Z, et al. (2000) Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. Am J Pathol 156: 1073–1083.PubMedCrossRefGoogle Scholar
  54. 54.
    Yoshii T, Fukumori T, Honjo Y, et al. (2002) Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. J Biol Chem 277: 6852–6857.PubMedCrossRefGoogle Scholar
  55. 55.
    Kim HR, Lin HM, Biliran H, et al. (1999) Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. Cancer Res 59: 4148–4154.PubMedGoogle Scholar
  56. 56.
    Oka N, Nakahara S, Takenaka Y, et al. (2005) Galectin-3 inhibits tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by activating Akt in human bladder carcinoma cells. Cancer Res 65: 7546–7553.PubMedGoogle Scholar
  57. 57.
    Lee YJ, Song YK, Song JJ, et al. (2003) Reconstitution of galectin-3 alters glutathione content and potentiates TRAIL-induced cytotoxicity by dephosphorylation of Akt. Exp Cell Res 288: 21–34.PubMedCrossRefGoogle Scholar
  58. 58.
    Stillman BN, Hsu DK, Pang M, et al. (2006) Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. J Immunol 176: 778–789.PubMedGoogle Scholar
  59. 59.
    Dong S and Hughes RC. (1996) Galectin-3 stimulates uptake of extracellular Ca2+ in human Jurkat T-cells. FEBS Lett 395: 165–169.PubMedCrossRefGoogle Scholar
  60. 60.
    Fukumori T, Takenaka Y, Yoshii T, et al. (2003) CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. Cancer Res 63: 8302–8311.PubMedGoogle Scholar
  61. 61.
    Yang RY, Hsu DK and Liu FT. (1996) Expression of galectin-3 modulates T-cell growth and apoptosis. Proc Natl Acad Sci U S A 93: 6737–6742.PubMedCrossRefGoogle Scholar
  62. 62.
    Yu F, Finley RL, Jr, Raz A, et al. (2002) Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation. J Biol Chem 277: 15819–15827.PubMedCrossRefGoogle Scholar
  63. 63.
    Matarrese P, Fusco O, Tinari N, et al. (2000) Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties. Int J Cancer 85: 545–554.PubMedCrossRefGoogle Scholar
  64. 64.
    Fukumori T, Takenaka Y, Oka N, et al. (2004) Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways. Cancer Res 64: 3376–3379.PubMedCrossRefGoogle Scholar
  65. 65.
    Akahani S, Nangia-Makker P, Inohara H, et al. (1997) Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res 57: 5272–5276.PubMedGoogle Scholar
  66. 66.
    Polyak K, Xia Y, Zweier JL, et al. (1997) A model for p53-induced apoptosis. Nature 389: 300–305.PubMedCrossRefGoogle Scholar
  67. 67.
    Bernerd F, Sarasin A and Magnaldo T. (1999) Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes. Proc Natl Acad Sci USA 96: 11329–11334.PubMedCrossRefGoogle Scholar
  68. 68.
    Kuwabara I, Kuwabara Y, Yang RY, et al. (2002) Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release. J Biol Chem 277: 3487–3497.PubMedCrossRefGoogle Scholar
  69. 69.
    Gendronneau G, Sidhu SS, Delacour D, et al. (2008) Galectin-7 in the control of epidermal homeostasis after injury. Mol Biol Cell 19: 5541–5549.PubMedCrossRefGoogle Scholar
  70. 70.
    Tribulatti MV, Mucci J, Cattaneo V, et al. (2007) Galectin-8 induces apoptosis in the CD4(high)CD8(high) thymocyte subpopulation. Glycobiology 17: 1404–1412.PubMedCrossRefGoogle Scholar
  71. 71.
    Norambuena A, Metz C, Vicuna L, et al. (2009) Galectin-8 induces apoptosis in Jurkat T cells by phosphatidic acid-mediated ERK1/2 activation supported by protein kinase A down-regulation. J Biol Chem 284: 12670–12679.PubMedCrossRefGoogle Scholar
  72. 72.
    Rabinovich GA, Modesti NM, Castagna LF, et al. (1997) Specific inhibition of lymphocyte proliferation and induction of apoptosis by CLL-I, a beta-galactoside-binding lectin. J Biochem 122: 365–373.PubMedCrossRefGoogle Scholar
  73. 73.
    Marth JD and Grewal PK. (2008) Mammalian glycosylation in immunity. Nat Rev Immunol 8: 874–887.PubMedCrossRefGoogle Scholar
  74. 74.
    Motran CC, Molinder KM, Liu SD, et al. (2008) Galectin-1 functions as a Th2 cytokine that selectively induces Th1 apoptosis and promotes Th2 function. Eur J Immunol 38: 3015–3027.PubMedCrossRefGoogle Scholar
  75. 75.
    Rabinovich GA, Ariel A, Hershkoviz R, et al. (1999) Specific inhibition of T-cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1. Immunology 97: 100–106.PubMedCrossRefGoogle Scholar
  76. 76.
    Rabinovich GA, Daly G, Dreja H, et al. (1999) Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis. J Exp Med 190: 385–398.PubMedCrossRefGoogle Scholar
  77. 77.
    Toscano MA, Commodaro AG, Ilarregui JM, et al. (2006) Galectin-1 suppresses autoimmune retinal disease by promoting concomitant Th2- and T regulatory-mediated anti-inflammatory responses. J Immunol 176: 6323–6332.PubMedGoogle Scholar
  78. 78.
    Stowell SR, Qian Y, Karmakar S, et al. (2008) Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion. J Immunol 180: 3091–3102.PubMedGoogle Scholar
  79. 79.
    Niwa H, Satoh T, Matsushima Y, et al. (2009) Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions: a potent therapeutic tool for Th1 and Th17-mediated skin inflammation. Clin Immunol 132: 184–194.PubMedCrossRefGoogle Scholar
  80. 80.
    Seki M, Oomizu S, Sakata KM, et al. (2008) Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol 127: 78–88.PubMedCrossRefGoogle Scholar
  81. 81.
    Rabinovich GA, Gabrilovich D and Sotomayor EM. (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25: 267–296.PubMedCrossRefGoogle Scholar
  82. 82.
    Liu SD, Tomassian T, Bruhn KW, et al. (2009) Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size. J Immunol 182: 5283–5295.PubMedCrossRefGoogle Scholar
  83. 83.
    Grigorian A, Torossian S and Demetriou M. (2009) T-cell growth, cell surface organization, and the galectin-glycoprotein lattice. Immunol Rev 230: 232–246.PubMedCrossRefGoogle Scholar
  84. 84.
    Lau KS, Partridge EA, Grigorian A, et al. (2007) Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129: 123–134.PubMedCrossRefGoogle Scholar
  85. 85.
    Demotte N, Stroobant V, Courtoy PJ, et al. (2008) Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. Immunity 28: 414–424.PubMedCrossRefGoogle Scholar
  86. 86.
    Clark AG, Chen S, Zhang H, et al. (2007) Multifunctional regulators of cell growth are differentially expressed in anergic murine B cells. Mol Immunol 44: 1274–1285.PubMedCrossRefGoogle Scholar
  87. 87.
    Sakaguchi S. (2004) Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22: 531–562.PubMedCrossRefGoogle Scholar
  88. 88.
    Curiel TJ, Coukos G, Zou L, et al. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10: 942–949.PubMedCrossRefGoogle Scholar
  89. 89.
    Zou W. (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6: 295–307.PubMedCrossRefGoogle Scholar
  90. 90.
    Garin MI, Chu CC, Golshayan D, et al. (2007) Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood 109: 2058–2065.PubMedCrossRefGoogle Scholar
  91. 91.
    Sugimoto N, Oida T, Hirota K, et al. (2006) Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int Immunol 18: 1197–1209.PubMedCrossRefGoogle Scholar
  92. 92.
    Wang J, Lu ZH, Gabius HJ, et al. (2009) Cross-linking of GM1 ganglioside by galectin-1 mediates regulatory T cell activity involving TRPC5 channel activation: possible role in suppressing experimental autoimmune encephalomyelitis. J Immunol 182: 4036–4045.PubMedCrossRefGoogle Scholar
  93. 93.
    Blois SM, Ilarregui JM, Tometten M, et al. (2007) A pivotal role for galectin-1 in fetomaternal tolerance. Nat Med 13: 1450–1457.PubMedCrossRefGoogle Scholar
  94. 94.
    Wang F, Wan L, Zhang C, et al. (2009) Tim-3-Galectin-9 pathway involves the suppression induced by CD4+CD25+ regulatory T cells. Immunobiology 214: 342–349.PubMedCrossRefGoogle Scholar
  95. 95.
    Guermonprez P, Valladeau J, Zitvogel L, et al. (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20: 621–667.PubMedCrossRefGoogle Scholar
  96. 96.
    Steinman RM, Hawiger D and Nussenzweig MC. (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21: 685–711.PubMedCrossRefGoogle Scholar
  97. 97.
    Reis e Sousa C. (2006) Dendritic cells in a mature age. Nat Rev Immunol 6: 476–483.PubMedCrossRefGoogle Scholar
  98. 98.
    Skoberne M, Beignon AS and Bhardwaj N. (2004) Danger signals: a time and space continuum. Trends Mol Med 10: 251–257.PubMedCrossRefGoogle Scholar
  99. 99.
    Svensson M, Maroof A, Ato M, et al. (2004) Stromal cells direct local differentiation of regu latory dendritic cells. Immunity 21: 805–816.PubMedCrossRefGoogle Scholar
  100. 100.
    Awasthi A, Carrier Y, Peron JP, et al. (2007) A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8: 1380–1389.PubMedCrossRefGoogle Scholar
  101. 101.
    Ilarregui JM, Croci DO, Bianco GA, et al. (2009) Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol 10: 981–991.PubMedCrossRefGoogle Scholar
  102. 102.
    Kotera Y, Shimizu K and Mule JJ. (2001) Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res 61: 8105–8109.PubMedGoogle Scholar
  103. 103.
    Fulcher JA, Chang MH, Wang S, et al. (2009) Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through Syk and protein kinase C signaling. J Biol Chem 284: 26860–26870.PubMedCrossRefGoogle Scholar
  104. 104.
    Hirashima M, Kashio Y, Nishi N, et al. (2009) Galectin-9 in physiological and pathological conditions. Glycoconj J 19: 593–600.CrossRefGoogle Scholar
  105. 105.
    Dai SY, Nakagawa R, Itoh A, et al. (2005) Galectin-9 induces maturation of human monocyte-derived dendritic cells. J Immunol 175: 2974–2981.PubMedGoogle Scholar
  106. 106.
    Anderson AC, Anderson DE, Bregoli L, et al. (2007) Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 318: 1141–1143.PubMedCrossRefGoogle Scholar
  107. 107.
    Hsu DK, Chernyavsky AI, Chen HY, et al. (2009) Endogenous galectin-3 is localized in membrane lipid rafts and regulates migration of dendritic cells. J Invest Dermatol 129: 573–583.PubMedCrossRefGoogle Scholar
  108. 108.
    Bernardes ES, Silva NM, Ruas LP, et al. (2006) Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity. Am J Pathol 168: 1910–1920.PubMedCrossRefGoogle Scholar
  109. 109.
    Breuilh L, Vanhoutte F, Fontaine J, et al. (2007) Galectin-3 modulates immune and inflammatory responses during helminthic infection: impact of galectin-3 deficiency on the functions of dendritic cells. Infect Immun 75: 5148–5157.PubMedCrossRefGoogle Scholar

Relevant Websites

  1. 110.
    Consortium for Functional Glycomics (
  2. 111.
    The Japanese Consortium for Glycobiology and Glycotechnology (

Copyright information

© Humana Press 2010

Authors and Affiliations

  1. 1.Laboratorio de Inmunopatología, Instituto de Biología y Medicina ExperimentalConsejo Nacional de Investigaciones Científicas y TécnicasBuenos AiresArgentina
  2. 2.Departamento de Química Biológica, Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina

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