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

Susanna Leskela,Hortensia De La Fuente,Francisco Sánchez-Madrid,Mónica Marazuela,Roberto González-Amaro,Ana Serrano,Ana Ramos-Levi,Ana Rodríguez-Muñoz,Miguel Sampedro-Nuñez

doi:10.1371/journal.pone.0123938

Abstract

IntroductionPatients 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 MethodsPeripheral 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.ResultsA 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.ConclusionsThe 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.

Highlights

MethodsPeripheral blood samples from 25 patients with Graves’ disease (GD), 11 Hashimoto’s thyroiditis (HT), and 24 healthy subjects were studied
Patients with autoimmune thyroid disease (AITD) show defects in their immune-regulatory mechanisms
A diminished expression of Gal-9, but not of Gal-1, by peripheral blood dendritic cells (DCs) was observed in Graves’ disease (GD) patients, mainly in those with Gravesophthalmopathy, and a significant negative association between disease severity and Gal-9 expression was detected

Summary

Methods

Peripheral blood samples from 25 patients with Graves’ disease (GD), 11 Hashimoto’s thyroiditis (HT), and 24 healthy subjects were studied. To explore the potential role of galectins in the immunopathogenesis of AITD, we first analyzed their expression in peripheral blood cDCs (CD11c+) and plasmacytoid DCs (pDCs, CD123+) from patients with HT and GD, and healthy controls by multi-parametric flow cytometry (Fig 1). No significant correlation was detected between Gal-9 expression by peripheral DCs and Gal-9 serum levels, either in patients or healthy controls (data not shown). When the expression of the Gal-9 ligand Tim-3 was analyzed in CD4+ and CD8+ T-lymphocytes, no significant differences doi:10.1371/journal.pone.0123938.g001 between patients and controls were detected (Fig 1F) and Tim-3 expression was not associated with clinical disease features or severity (data not shown)

Results

Discussion

Conclusion