title: Galectin-1 triggers an immunoregulatory signature in Th cells functionally defined by IL-10 expression.
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.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Filiberto
authors.initials: F
authors.lastname: Cedeno-Laurent
authors.forename: Matthew
authors.initials: M
authors.lastname: Opperman
authors.forename: Steven R
authors.initials: SR
authors.lastname: Barthel
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dimitroff
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000628:therapy; D019281:Dimerization; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014157:Transcription Factors / Q000502:physiology; D019139:Tumor Escape / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D037483:Galectin 1; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016753:Interleukin-10