Cell-Surface Glycoconjugates Controlling Human T-Lymphocyte Homing: Implications for Bronchial Asthma and Atopic Dermatitis

  • Reiji Kannagi
  • Keiichiro Sakuma
  • Katsuyuki Ohmori
Conference paper


Cell-surface glycans play important roles in lymphocyte traffic and homing. Cell adhesion mediated by glycans, such as selectin-mediated cell adhesion, is involved in the first step of every process of extravasation of leukocytes, either in granulocytes or in lymphocytes (Fig. 1). Glycan-mediated cell adhesion is virtually an only one cell-adhesion system that tolerates a strong shear force of normal blood flow in the general circulation. This step is crucial for every leukocyte diapedesis; without glycan-mediated cell adhesion, other secondary proteinaceous cell-adhesion molecules such as integrins or the Ig superfamily do not operate effectively. Recently, it has become increasingly clear that homing processes of various subsets of T lymphocytes are elegantly regulated by different species of cell-adhesive glycans, and alterations in glycan expression are closely associated with the pathophysiology of several well-known human diseases.


Atopic Dermatitis Sialic Acid Peripheral Lymph Node High Endothelial Venule Selectin Ligand 



This work was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (24590364 and on innovative areas 23112520), grants-in-aid for young scientists from the Japan Society for the Promotion of Science (20790583 and 22790774), grants-in-aid for the Third-Term Comprehensive Ten-year Strategy for Cancer Control from the Ministry of Health and Welfare, and a grant from the Uehara Memorial Foundation, Japan.


  1. 1.
    Lowe JB, Stoolman LM, Nair RP, Larsen RD, Berhend TL, Marks RM (1990) ELAM-1-dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell 63:475–484CrossRefPubMedGoogle Scholar
  2. 2.
    Phillips ML, Nudelman E, Gaeta FCA, Perez M, Singhal AK, Hakomori S, Paulson JC (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science 250:1130–1132CrossRefPubMedGoogle Scholar
  3. 3.
    Walz G, Aruffo A, Kolanus W, Bevilacqua M, Seed B (1990) Recognition by ELAM-1 of the sialyl-Lexdeterminant on myeloid and tumor cells. Science 250:1132–1135CrossRefPubMedGoogle Scholar
  4. 4.
    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 273:11225–11233CrossRefPubMedGoogle Scholar
  5. 5.
    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 α1  →  3 fucosyltransferase VII and newly cloned GlcNAcβ 6-sulfotransferase cDNA. Proc Natl Acad Sci USA 96:4530–4535CrossRefPubMedGoogle Scholar
  6. 6.
    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 107:3197–3204CrossRefPubMedGoogle Scholar
  7. 7.
    Sallusto F, Lanzavecchia A (2009) Heterogeneity of CD4+memory T cells: functional modules for tailored immunity. Eur J Immunol 39:2076–2082CrossRefPubMedGoogle Scholar
  8. 8.
    Sallusto F, Baggiolini M (2008) Chemokines and leukocyte traffic. Nat Immunol 9:949–952CrossRefPubMedGoogle Scholar
  9. 9.
    Campbell JJ, Clark RA, Watanabe R, Kupper TS (2010) Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 116:767–771CrossRefPubMedGoogle Scholar
  10. 10.
    Santamaria-Babi LF (2006) Skin-homing T cells in cutaneous allergic inflammation. Chem Immunol Allergy 91:87–97CrossRefPubMedGoogle Scholar
  11. 11.
    Santamaria-Babi LF (2004) CLA+T cells in cutaneous diseases. Eur J Dermatol 14:13–18PubMedGoogle Scholar
  12. 12.
    Seneviratne SL, Black AP, Jones L, Bailey AS, Ogg GS (2007) The role of skin-homing T cells in extrinsic atopic dermatitis. Q J Med 100:19–27CrossRefGoogle Scholar
  13. 13.
    Bateman EA, Ardern-Jones MR, Ogg GS (2006) Persistent central memory phenotype of ­circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+T cells. J Allergy Clin Immunol 118:1350–1356CrossRefPubMedGoogle Scholar
  14. 14.
    Kannagi R (2001) Transcriptional regulation of expression of carbohydrate ligands for cell adhesion molecules in the selectin family. Adv Exp Med Biol 491:267–278CrossRefPubMedGoogle Scholar
  15. 15.
    Chen G-Y, Osada H, Santamaria-Babi LF, Kannagi R (2006) Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. Proc Natl Acad Sci USA 103:16894–16899CrossRefPubMedGoogle Scholar
  16. 16.
    Chen G-Y, Sakuma K, Kannagi R (2008) Significance of NF-κB/GATA axis in TNF-α-induced expression of 6-sulfated cell-recognition glycans in human T-lymphocytes. J Biol Chem 283:34563–34570CrossRefPubMedGoogle Scholar
  17. 17.
    Sakuma K, Chen GY, Aoki M, Kannagi R (2012) Induction of 6-sulfated glycans with cell adhesion activity via T-bet and GATA-3 in human helper T cells. Biochem Biophys Acta 1820:841–848CrossRefPubMedGoogle Scholar
  18. 18.
    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 USA 96:1597–1602CrossRefPubMedGoogle Scholar
  19. 19.
    Kannagi R (2002) Regulatory roles of carbohydrate ligands for selectins in homing of lymphocytes. Curr Opin Struct Biol 12:599–608CrossRefPubMedGoogle Scholar
  20. 20.
    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 60:1410–1416PubMedGoogle Scholar

Copyright information

© Springer 2012

Authors and Affiliations

  • Reiji Kannagi
    • 1
    • 2
  • Keiichiro Sakuma
    • 1
    • 2
  • Katsuyuki Ohmori
    • 3
  1. 1.Research Complex for Medical FrontiersAichi Medical UniversityNagakute, AichiJapan
  2. 2.Department of Molecular PathologyAichi Cancer CenterNagoyaJapan
  3. 3.Department of Clinical PathologyKyoto University School of MedicineKyotoJapan

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