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Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death

Nature Immunology volume 8, pages 825834 (2007) | Download Citation

Abstract

Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (TH1), TH2 or interleukin 17–producing T helper (TH-17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although TH1- and TH-17–differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1–induced cell death, TH2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1–deficient mice developed greater TH1 and TH-17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response.

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Acknowledgements

We thank H. Rosenberg for critical reading of the manuscript; J. Hirabayashi, K.I Kasai and F.T. Liu for plasmids; C. Stanley, L. Campagna, M. Barboza, M. Vermeulen and the staff of the Animal Facility (Facultad de Ciencias Exactas y Naturales, University of Buenos Aires) for technical assistance; and G. Vasta, L. Steinman, M. Lenardo, L. Glimcher, R. Schreiber, C. Weaver, N. Rubinstein, L. Fainboim and J. Geffner for comments or advice. Rabbit antiserum to ST6Gal1 was from K. Colley (University of Illinois, Chicago) and endotoxin-free SEA was from M. Doenhoff (University of Wales). Supported by the Cancer Research Institute (G.A.R.), the Mizutani Foundation for Glycoscience (G.A.R.), the Sales Foundation (G.A.R.), the National Agency for Promotion of Science and Technology (G.A.R.), the Wellcome Trust (G.A.R. and E.M.R.), the University of Buenos Aires (G.A.R.), the Bunge & Born Foundation (G.A.R.), the Fiorini Foundation (G.A.R.), the National Institutes of Health (L.G.B. and J.D.H.), Ligue Contre le Cancer (F.P.), the John Simon Guggenheim Memorial Foundation (G.A.R.) and The National Research Council for Scientific and Technical Investigations (G.A.R. and N.W.Z.).

Author information

Author notes

    • Marta A Toscano
    • , Germán A Bianco
    • , Juan M Ilarregui
    • , Diego O Croci
    • , Norberto W Zwirner
    •  & Gabriel A Rabinovich

    Present address: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas and Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428ADN Buenos Aires, Argentina.

    • Germán A Bianco
    •  & Juan M Ilarregui

    These authors equally contributed to this work.

Affiliations

  1. División de Immunogenética. Hospital de Clínicas 'José de San Martín', Facultad de Medicina, Universidad de Buenos Aires, C1120AAF Buenos Aires, Argentina.

    • Marta A Toscano
    • , Germán A Bianco
    • , Juan M Ilarregui
    • , Diego O Croci
    • , Norberto W Zwirner
    •  & Gabriel A Rabinovich
  2. Departamento de Neurología, Instituto de Investigaciones Neurológicas 'Dr. Raul Carrea', C1428 Buenos Aires, Argentina.

    • Jorge Correale
  3. Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.

    • Joseph D Hernandez
    •  & Linda G Baum
  4. Institut Jacques Monod, Unités Mixtes de Recherche-Centre National de la Recherche Scientifique 7592, Paris 6 and Paris 7 Universities, 75251 Paris, France.

    • Francoise Poirier
  5. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1 E7HT, UK.

    • Eleanor M Riley

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Contributions

M.A.T. designed and did experiments and contributed to manuscript preparation; G.A.B. and J.M.I. designed and did experiments; D.O.C. assisted with histological data; J.C. assisted with EAE experiments; F.P. provided Lgals1−/− mice and advice; N.W.Z., J.D.H., L.G.B. and E.M.R. contributed reagents and to the design of experiments and writing of the manuscript; and G.A.R. conceptualized and supervised the work, designed the experiments and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gabriel A Rabinovich.

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DOI

https://doi.org/10.1038/ni1482

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