Abstract
Galectin-1 (Gal-1), a β-galactoside-binding protein, can alter fate and effector function of Th cells; however, little is known about how Gal-1 induces Th cell differentiation. In this article, we show that both uncommitted and polarized Th cells bound by Gal-1 expressed an immunoregulatory signature defined by IL-10. IL-10 synthesis was stimulated by direct Gal-1 engagement to cell surface glycoproteins, principally CD45, on activated Th cells and enhanced by IL-21 expression through the c-Maf/aryl hydrocarbon receptor pathway, independent of APCs. Gal-1-induced IL-10(+) T cells efficiently suppressed T cell proliferation and T cell-mediated inflammation and promoted the establishment of cancer immune-privileged sites. Collectively, these findings show how Gal-1 functions as a major glycome determinant regulating Th cell development, inflammation, and tumor immunity.
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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Antibodies, Monoclonal / pharmacology
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Cytokines / biosynthesis
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Cytokines / genetics
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Dermatitis, Allergic Contact / immunology
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Dermatitis, Allergic Contact / therapy
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Dimerization
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Galectin 1 / antagonists & inhibitors
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Galectin 1 / genetics
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Galectin 1 / immunology
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Galectin 1 / pharmacology*
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Gene Expression Regulation / immunology*
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Humans
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Immune Tolerance
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Immunoglobulin Fc Fragments / genetics
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Immunoglobulin Fc Fragments / immunology
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Interleukin-10 / deficiency
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Interleukin-10 / metabolism*
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Melanoma, Experimental / immunology
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Melanoma, Experimental / therapy
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Mice
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Mice, Inbred C57BL
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Neoplasm Transplantation
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Recombinant Fusion Proteins / pharmacology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Helper-Inducer / transplantation
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Transcription Factors / physiology
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Tumor Escape / immunology
Substances
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Antibodies, Monoclonal
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Cytokines
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Galectin 1
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Immunoglobulin Fc Fragments
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Recombinant Fusion Proteins
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Transcription Factors
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Interleukin-10