Skip to main content

Sialyl Sulfoglycans in Immune Regulation and Their Clinical Applications

  • Reference work entry
  • First Online:
Glycoscience: Biology and Medicine

Abstract

Several sialyl sulfoglycans in human cells and tissues have recently been found to serve as specific ligands for carbohydrate-recognition molecules in the selectin and siglec families and are expected to play crucial roles in the regulation of immune cell functions in health and diseases. One such sialyl sulfoglycan, sialyl 6-sulfo Lewis X, can serve as a ligand for all members of the selectin family and siglec-7. This glycan was known to be expressed in skin-homing central helper memory T-cells which exhibited bidirectional homing behavior to the skin and peripheral lymph nodes, and was recently found to be involved in the pathophysiology of atopic dermatitis. The binding activity of this glycan to selectins and siglecs is regulated by cyclization of the terminal sialic acid residue, and examination of T-cell subsets expressing sialyl 6-sulfo Lewis X with normal and cyclic sialic acid residues in peripheral blood of the patients is proposed to be clinically useful in evaluating the risk of atopic dermatitis recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 899.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Berg EL, Yoshino T, Rott LS, Robinson MK, Warnock RA, Kishimoto TK, Picker LJ, Butcher EC (1991) The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med 174:1461–1466

    Article  CAS  PubMed  Google Scholar 

  • Chen G-Y, Sakuma K, Kannagi R (2008) Significance of NF-kappaB/GATA axis in TNF-α-induced expression of 6-sulfated cell-recognition glycans in human T-lymphocytes. J Biol Chem 283:34563–34570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costantini C, Calzetti F, Perbellini O, Micheletti A, Scarponi C, Lonardi S, Pelletier M, Schäkel K, Pizzolo G, Facchetti F, Vermi W, Albanesi C, Cassatella MA (2011) Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFNγ: role of CD18, ICAM-1, and ICAM-3. Blood 117:1677–1686

    Article  CAS  PubMed  Google Scholar 

  • Groux-Degroote S, Krzewinski-Recchi MA, Cazet A, Vincent A, Lehoux S, Lafitte JJ, Van Seuningen I, Delannoy P (2008) IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated Lewis X epitopes in the human bronchial mucosa. Biochem J 410:213–223

    Article  CAS  PubMed  Google Scholar 

  • Günther C, Blau K, Forster U, Viehweg A, Wozel G, Schäkel K (2013) Reduction of inflammatory slan (6-sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept. Exp Dermatol 22:535–540

    Article  PubMed  Google Scholar 

  • Hansel A, Gunther C, Baran W, Bidier M, Lorenz HM, Schmitz M, Bachmann M, Dobel T, Enk AH, Schäkel K (2012) Human 6-sulfo LacNAc (slan) dendritic cells have molecular and functional features of an important pro-inflammatory cell type in lupus erythematosus. J Autoimmun 40:1–8

    Article  PubMed  Google Scholar 

  • Izawa M, Kumamoto K, Mitsuoka C, Kanamori A, Ohmori K, Ishida H, Nakamura S, Kurata-Miura K, Sasaki K, Nishi T, Kannagi R (2000) Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer. Cancer Res 60:1410–1416

    CAS  PubMed  Google Scholar 

  • Kannagi R (2002) Regulatory roles of carbohydrate ligands for selectins in homing of lymphocytes. Curr Opin Struct Biol 12:599–608

    Article  CAS  PubMed  Google Scholar 

  • Kannagi R, Ohmori K (2008) Carbohydrate ligands for selectins in immune cell trafficking. In: Taniguchi N, Suzuki A, Ito Y, Narimatsu H, Kawasaki K, Hase S (eds) Experimental glycoscience, glycobiology. Springer, Tokyo, pp 148–153

    Chapter  Google Scholar 

  • Kannagi R, Ohmori K, Chen GY, Miyazaki K, Izawa M, Sakuma K (2011) Sialylated and sulfated carbohydrate ligands for selectins and siglecs: involvement in traffic and homing of human memory T and B lymphocytes. Adv Exp Med Biol 705:549–569

    Article  CAS  PubMed  Google Scholar 

  • Kannagi R, Sakuma K, Ohmori K (2013) Cell-surface glycoconjugates controlling human T-lymphocyte homing: implications for bronchial asthma and atopic dermatitis. In: Shibasaki M, Iino M, Osada H (eds) Chembiomolecular science: at the Frontier of chemistry and biology. Springer, Tokyo, pp 167–176

    Google Scholar 

  • Kimura N, Mitsuoka C, Kanamori A, Hiraiwa N, Uchimura K, Muramatsu T, Tamatani T, Kansas GS, Kannagi R (1999) Reconstitution of functional l-selectin ligands on a cultured human endothelial cell line by co-transfection of α-3 fucosyltransferase VII and newly cloned GlcNAcβ: 6-sulfotransferase cDNA. Proc Natl Acad Sci U S A 96:4530–4535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimura N, Ohmori K, Miyazaki K, Izawa M, Matsuzaki Y, Yasuda Y, Takematsu H, Kozutsumi Y, Moriyama A, Kannagi R (2007) Human B-lymphocytes express α2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/siglec-2. J Biol Chem 282:32200–32207

    Article  CAS  PubMed  Google Scholar 

  • Mitsuoka C, Sawada-Kasugai M, Ando-Furui K, Izawa M, Nakanishi H, Nakamura S, Ishida H, Kiso M, Kannagi R (1998) Identification of a major carbohydrate capping group of the l-selectin ligand on high endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis X. J Biol Chem 273:11225–11233

    Article  CAS  PubMed  Google Scholar 

  • Mitsuoka C, Ohmori K, Kimura N, Kanamori A, Komba S, Ishida H, Kiso M, Kannagi R (1999) Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes. Proc Natl Acad Sci U S A 96:1597–1602

    Google Scholar 

  • Miyazaki K, Sakuma K, Kawamura YI, Izawa M, Ohmori K, Mitsuki M, Yamaji T, Hashimoto Y, Suzuki A, Saito Y, Dohi T, Kannagi R (2012) Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors, siglec-7 and -9. J Immunol 188:4690–4700

    Article  CAS  PubMed  Google Scholar 

  • Ohmori K, Takada A, Ohwaki I, Takahashi N, Furukawa Y, Maeda M, Kiso M, Hasegawa A, Kannagi M, Kannagi R (1993) A distinct type of sialyl Lewis X antigen defined by a novel monoclonal antibody is selectively expressed on helper memory T cells. Blood 82:2797–2805

    CAS  PubMed  Google Scholar 

  • Ohmori K, Kanda K, Mitsuoka C, Kanamori A, Kurata-Miura K, Sasaki K, Nishi T, Tamatani T, Kannagi R (2000) p- and e-selectins recognize sialyl 6-sulfo Lewis X, the recently-identified l-selectin ligand. Biochem Biophys Res Commun 278:90–96

    Article  CAS  PubMed  Google Scholar 

  • Ohmori K, Fukui F, Kiso M, Imai T, Yoshie O, Hasegawa H, Matsushima K, Kannagi R (2006) Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis X, a selectin ligand expressed on a subset of skin-homing helper memory T cells. Blood 107:3197–3204

    Article  CAS  PubMed  Google Scholar 

  • Sakuma K, Chen GY, Aoki M, Kannagi R (2012a) Induction of 6-sulfated glycans with cell adhesion activity via T-bet and GATA-3 in human helper T cells. Biochim Biophys Acta 1820:841–848

    Article  CAS  PubMed  Google Scholar 

  • Sakuma K, Furuhashi T, Kondo S, Yabe U, Ohmori K, Ito H, Aoki M, Morita A, Kannagi R (2012b) Sialic acid cyclization of human Th homing receptor glycan associated with recurrent exacerbations of atopic dermatitis. J Dermatol Sci 68:187–193

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763

    Article  CAS  PubMed  Google Scholar 

  • Schäkel K, Kannagi R, Kniep B, Goto Y, Mitsuoka C, Zwirner J, Soruri A, von Kietzell M, Rieber EP (2002) 6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells. Immunity 17:289–301

    Article  PubMed  Google Scholar 

  • Wakabayashi C, Adachi T, Wienands J, Tsubata T (2002) A distinct signaling pathway used by the IgG-containing B cell antigen receptor. Science 298:2392–2395

    Article  CAS  PubMed  Google Scholar 

  • Yusa A, Miyazaki K, Kimura N, Izawa M, Kannagi R (2010) Epigenetic silencing of the sulfate transporter gene DTDST induces sialyl Lewisx expression and accelerates proliferation of colon cancer cells. Cancer Res 70:4064–4073

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Reiji Kannagi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this entry

Cite this entry

Kannagi, R., Sakuma, K., Ohmori, K. (2015). Sialyl Sulfoglycans in Immune Regulation and Their Clinical Applications. In: Taniguchi, N., Endo, T., Hart, G., Seeberger, P., Wong, CH. (eds) Glycoscience: Biology and Medicine. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54841-6_129

Download citation

Publish with us

Policies and ethics