title: Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients.
abstract: Galectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on different cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its effects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this effect is counteracted by the anti-Gal-8 autoantibodies. Given that Gal-8 can potentially interact with several glycoproteins, here we analyzed the β2 integrin Lymphocyte Function-Associated Antigen-1 (LFA-1), which is involved in leukocyte cell adhesion and immunological synapses. We show by GST-pull down assays that Gal-8 interacts with LFA-1 and this interaction is inhibited by anti-Gal-8 autoantibodies isolated from SLE patients. In cell adhesion assays, Gal-8 precluded the interaction of LFA-1 with its ligand Intracellular Adhesion Molecule-1 (ICAM-1). These results suggest that Gal-8 can exert immunosuppressive action not only by inducing apoptosis in activated T cells but also by negatively modulating the crucial function of LFA-1 in the immune system, while function-blocking autoantibodies counteract these effects.
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Lucas
authors.initials: L
authors.lastname: Vicuña
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Pardo
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Curkovic
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Remziye
authors.initials: R
authors.lastname: Döger
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Claudia
authors.initials: C
authors.lastname: Oyanadel
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Claudia
authors.initials: C
authors.lastname: Metz
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Loreto
authors.initials: L
authors.lastname: Massardo
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Alfonso
authors.initials: A
authors.lastname: González
authors.affiliation: Departamento de Inmunología Clínica y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, amsoza@med.puc.cl.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soza
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D037161:Galectins; C091991:LGALS8 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1