title: Graves' disease is associated with a defective expression of the immune regulatory molecule galectin-9 in antigen-presenting dendritic cells.
abstract: BACKGROUND
  Patients with autoimmune thyroid disease (AITD) show defects in their immune-regulatory mechanisms. Herein we assessed the expression and function of galectin-1 and galectin-9 (Gal-1, Gal-9) in dendritic cells (DCs) from patients with AITD.
  
  
  METHODS
  Peripheral blood samples from 25 patients with Graves' disease (GD), 11 Hashimoto's thyroiditis (HT), and 24 healthy subjects were studied. Thyroid tissue samples from 44 patients with AITD and 22 patients with goiter were also analyzed. Expression and function of Gal-1 and Gal-9 was assessed by quantitative RT-PCR, immunofluorescence and flow cytometry.
  
  
  RESULTS
  A diminished expression of Gal-9, but not of Gal-1, by peripheral blood DCs was observed in GD patients, mainly in those with Graves´ ophthalmopathy, and a significant negative association between disease severity and Gal-9 expression was detected. In addition, the mRNA levels of Gal-9 and its ligand TIM-3 were increased in thyroid tissue from AITD patients and its expression was associated with the levels of Th1/Th12/Th17 cytokines. Immunofluorescence studies proved that intrathyroidal Gal-9 expression was confined to DCs and macrophages. Finally, in vitro functional assays showed that exogenous Gal-9 had a suppressive effect on the release of Th1/Th2/Th17 cytokines by DC/lymphocyte autologous co-cultures from both AITD patients and healthy controls.
  
  
  CONCLUSIONS
  The altered pattern of expression of Gal-9 in peripheral blood DCs from GD patients, its correlation with disease severity as well as its ability to suppress cytokine release suggest that Gal-9 could be involved in the pathogenesis of AITD.
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Leskela
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Serrano
authors.affiliation: Department of Immunology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: de la Fuente
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodríguez-Muñoz
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos-Levi
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sampedro-Nuñez
authors.affiliation: Department of Immunology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: Department of Immunology, School of Medicine, UASLP, San Luis Potosí, SLP, México.
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
authors.affiliation: Department of Endocrinology, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Marazuela
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037161:Galectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006042:Goiter / Q000276:immunology; D006111:Graves Disease / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
chemical_list: D016207:Cytokines; D037483:Galectin 1; D037161:Galectins; C445499:LGALS1 protein, human; C105032:LGALS9 protein, human