Graves' disease is associated with a defective expression of the immune regulatory molecule galectin-9 in antigen-presenting dendritic cells

PLoS One. 2015 Apr 16;10(4):e0123938. doi: 10.1371/journal.pone.0123938. eCollection 2015.

Abstract

Introduction: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Female
  • Galectin 1 / genetics
  • Galectin 1 / immunology
  • Galectin 1 / metabolism
  • Galectins / genetics
  • Galectins / immunology
  • Galectins / metabolism*
  • Galectins / pharmacology
  • Goiter / immunology
  • Graves Disease / immunology*
  • Hashimoto Disease / immunology
  • Humans
  • Male
  • Middle Aged
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Thyroiditis, Autoimmune / immunology*

Substances

  • Cytokines
  • Galectin 1
  • Galectins
  • LGALS1 protein, human
  • LGALS9 protein, human

Grants and funding

This work was supported by grants from the Fondo de Investigaciones Sanitarias (FISS) PI10/02521 and S2010/BMD-2328 TIRONET (Comunidad de Madrid), Spain (to MM) and the Fondo de Cooperación Internacional en Ciencia y Tecnología (FONCICYT) 95395, European Union-México (to RGA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.