Analysis of the cumulative changes in Graves’ disease thyroid glands points to IFN signature, plasmacytoid DCs and alternatively activated macrophages as chronicity determining factors

Ruiz-Riol, Marta; Barnils, Maria del Pilar Armengol; Colobran, Roger; Sánchez-Pla, Álex; Serres, Francesc-E. Borràs; Lucas-Martín, Anna; Martínez-Cáceres, Eva; Pujol-Borrell, Ricardo

doi:10.1016/j.jaut.2011.01.002

Cited by 33 publications

(18 citation statements)

References 59 publications

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“…This is one mechanism by which the virus can evade immune surveillance, resulting in viral persistence. The PDC numbers observed in the present study are consistent with those reported by RuizRiol et al, who showed increased expression of IFN1 genes in the thyroid tissues of patients with GD (33). However, there is still no real evidence that this occurs in response to viral infection.…”

supporting

confidence: 93%

Immunological Changes and Increased Expression of Myxovirus Resistance Protein A in Thyroid Tissue of Patients with Recent Onset and Untreated Graves' Disease

Hammerstad

Jahnsen

Tauriainen

et al. 2014

Thyroid

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The increase in CD8+ T cells during the chronic stage of GD suggests that they may play a role in progression of the autoimmune process from early to chronic thyroiditis. Upregulation of MxA expression during the early stages of the disease, and the positive correlation between the number of PDCs and the number of MxA+ leucocytes, suggests that activated PDCs secrete type I IFNs at the lesion site, possibly in response to viral infection.

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supporting

confidence: 93%

Immunological Changes and Increased Expression of Myxovirus Resistance Protein A in Thyroid Tissue of Patients with Recent Onset and Untreated Graves' Disease

Hammerstad

Jahnsen

Tauriainen

et al. 2014

Thyroid

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“…An analysis of gene expression pattern in GD thyroid tissue using a gene chip system revealed disease stage dependent (short vs. long course GD) regulation of many genes associated with immune system including induction of lineage specific antigens of T-and B-cells, macrophages, as well as DCs in long course GD. Immunofluorescence analysis of thyroid specimens confirmed the presence of CD303 + CD123 + CD83 -immature pDCs typically in close contact with lymphocytes, as well as CD11c + cDCs, which were also identified as a potential local source of IFNa [43]. Disease stage dependent changes in the structure of thyroid immune infiltrates was also shown by Hammerstad and colleagues in immunostaining assays of thyroid tissue obtained both from HT [44] and GD patients [45].…”

Section: Cd8asupporting

confidence: 53%

Dendritic cells in autoimmune disorders and cancer of the thyroid

Lewiński

Śliwka

Stasiołek

2014

Folia Histochem Cytobiol.

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Dendritic cells (DCs), considered as one of the crucial immune regulatory populations, are implicated in the immune pathology of various disorders. Also in the thyroid gland, DCs were shown to be involved in early and chronic phases of various types of autoimmunity -including Hashimoto's thyroiditis and Graves' disease. In thyroid malignant processes, DCs are suggested as an important element of both tumour defence and tumour immune evasion mechanisms. Recent findings emphasize a crucial role of interactions between particular DC subsets and other regulatory cell populations (e.g. FoxP3+ regulatory T cells) in thyroid pathology. Additionally, an increasing attention has been paid to the control of DC function by thyrometabolic conditions.

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“…Immunohistopathological changes occurring in the thyroid gland of GD patients, such as inappropriate HLA expression (5) and the formation of tertiary lymphoid tissue (6), are similar to those found in chronic infections (7), suggesting that the intrathyroidal immune response is important for disease pathogenesis (8). Genome-wide transcriptomic analysis of GD thyroid tissue showed a strong IFN signature (9,10) and a pattern of immune system-related genes of progressive complexity over time, supporting the importance of thyroid-centered mechanisms in chronification (11).…”

mentioning

confidence: 98%

Graves’ Disease TSHR-Stimulating Antibodies (TSAbs) Induce the Activation of Immature Thymocytes: A Clue to the Riddle of TSAbs Generation?

Giménez‐Barcons

Colobran

Gómez-Pau

et al. 2015

The Journal of Immunology

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Graves’ disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients. We previously demonstrated that TSHR, the target of this autoimmune response, is also a key susceptibility gene for GD, probably acting through thymic-dependent central tolerance. We also showed that TSHR is, unexpectedly, expressed in thymocytes. In this report, we confirm the expression of TSHR in thymocytes by protein immunoblotting and quantitative PCR, and show that expression is confined to maturing thymocytes. Using functional assays, we show that thymic TSHR is functional and that TSAbs can stimulate thymocytes through this receptor. This new activity of TSAbs on thymocytes may: 1) explain GD-associated thymic enlargement (hyperplasia), and 2) suggest the provocative hypothesis that the continuous stimulation of thymocytes by TSAbs could lead to a vicious cycle of iterative improvement of the affinity and stimulating capability of initially low-affinity antibacterial (e.g., Yersinia) Abs cross-reactive with TSHR, eventually leading to TSAbs. This may help to fill one of the gaps in our present understanding of unusual characteristics of TSAbs.

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Analysis of the cumulative changes in Graves’ disease thyroid glands points to IFN signature, plasmacytoid DCs and alternatively activated macrophages as chronicity determining factors

Cited by 33 publications

References 59 publications

Immunological Changes and Increased Expression of Myxovirus Resistance Protein A in Thyroid Tissue of Patients with Recent Onset and Untreated Graves' Disease

Immunological Changes and Increased Expression of Myxovirus Resistance Protein A in Thyroid Tissue of Patients with Recent Onset and Untreated Graves' Disease

Dendritic cells in autoimmune disorders and cancer of the thyroid

Graves’ Disease TSHR-Stimulating Antibodies (TSAbs) Induce the Activation of Immature Thymocytes: A Clue to the Riddle of TSAbs Generation?

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