title: Galectin-1 and -3 gene silencing in immature and mature dendritic cells enhances T cell activation and interferon-γ production.
abstract: DCs are specialized APCs capable of inducing T cell activation as well as promoting tolerance. Although Gal, a family of β-galactoside-binding proteins, were found to affect immunity, little is known about the contribution of DC-expressed Gal on T cell activation. Here, we show that human imDCs and mDCs constitutively express Gal-1, Gal-3, Gal-8, and Gal-9 at mRNA and protein levels. Two of the most abundant Gal-Gal-1 and Gal-3-were highly expressed and detected on the cell surface of DCs. In contrast to Gal-8, knockdown of Gal-1 or Gal-3 in DCs enhanced allogeneic T cell responses. This was observed with imDCs and mDCs, but the effects were more pronounced with imDCs. Furthermore, allogeneic CD4(+) T cells incubated with Gal-1 or Gal-3 knockdown DCs produced more IFN-γ and less IL-10 than did control cells. The percentage of apoptotic T cells was significantly higher in cultures with control DCs than that with Gal-1 or Gal-3 knockdown DCs. Collectively, the data indicate that DC-expressed Gal-1 and Gal-3 are regulatory molecules that favor the inhibition of T cell activation. Furthermore, the data provide a new mechanism for the poor capacity of imDCs to stimulate T cells.
authors.affiliation: Department of Immunology, Institute for Cancer Research, Radiumhospitalet-Rikshospitalet University Hospital, Montebello, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Mobergslien
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D037483:Galectin 1 / Q000235:genetics*; D037502:Galectin 3 / Q000235:genetics*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D037483:Galectin 1; D037502:Galectin 3; D007371:Interferon-gamma