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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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.).
The authors declare no competing financial interests.
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Toscano, M., Bianco, G., Ilarregui, J. et al. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8, 825–834 (2007). https://doi.org/10.1038/ni1482
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