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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Apoptosis / immunology*
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Cell Differentiation / immunology
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Flow Cytometry
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Galectin 1 / genetics
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Galectin 1 / immunology*
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Galectin 1 / metabolism
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Glycosylation
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Humans
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Immunoblotting
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In Situ Nick-End Labeling
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Inflammation / immunology*
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Inflammation / metabolism
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Interleukin-17 / metabolism
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Mice
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Polysaccharides / immunology
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Polysaccharides / metabolism
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / metabolism*
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T-Lymphocytes, Helper-Inducer / pathology
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Th1 Cells / cytology
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Th1 Cells / metabolism
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Th1 Cells / pathology
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Th2 Cells / cytology
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Th2 Cells / metabolism
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Th2 Cells / pathology
Substances
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Galectin 1
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Interleukin-17
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Membrane Glycoproteins
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Polysaccharides