Regulatory T cells but not T helper 17 cells are modulated in an animal model of Graves’ hyperthyroidism

Zhou, Jin; Bi, Mei; Fan, Chenling; Song, Xizhu; Yang, Rong; Zhao, Shujie; Li, Li; Li, Yushu; Wang, Teng; Shan, Zhongyan

doi:10.1007/s10238-011-0137-6

Cited by 32 publications

(18 citation statements)

References 26 publications

(25 reference statements)

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“…Even though we do not have a commendable explanation for our result that Th17 is not associated with this GD model, it is feasible that it could be due, at least in part, to the different genetic background of the individuals studied, the presence or absence of opthalmopathy, and the stage of the disease. The balance between Treg and Th17 cells may control inflammation and be important in the pathogenesis of GD (Zhou et al 2012). To assess whether this balance was broken in an animal model of Graves' hyperthyroidism, we detected Th17/Treg functions on different levels including cell frequencies and key transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease

Wang

et al. 2013

Journal of Endocrinology

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Graves' disease (GD) is a common organ-specific autoimmune disease with the prevalence between 0.5 and 2% in women. Several lines of evidence indicate that the shed A-subunit rather than the full-length thyrotropin receptor (TSHR) is the autoantigen that triggers autoimmunity and leads to hyperthyroidism. We have for the first time induced GD in female rhesus monkeys, which exhibit greater similarity to patients with GD than previous rodent models. After final immunization, the monkeys injected with adenovirus expressing the A-subunit of TSHR (A-sub-Ad) showed some characteristics of GD. When compared with controls, all the test monkeys had significantly higher TSHR antibody levels, half of them had increased total thyroxine (T 4 ) and free T 4 , and 50% developed goiter. To better understand the underlying mechanisms, quantitative studies on subpopulations of CD4CT helper cells were carried out. The data indicated that this GD model involved a mixed Th1 and Th2 response. Declined Treg proportions and increased Th17:Treg ratio are also observed. Our rhesus monkey model successfully mimicked GD in humans in many aspects. It would be a useful tool for furthering our understanding of the pathogenesis of GD and would potentially shorten the distance toward the prevention and treatment of this disease in human.

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Section: Discussionmentioning

confidence: 99%

Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease

Wang

et al. 2013

Journal of Endocrinology

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“…However, the Th2 theory cannot explain all conditions. Recently, researchers have recognized that two other CD4 + T cell subsets and one B cell subtype, namely, the Th17 and regulatory T (Treg) cells, along with regulatory B (Breg) cells, may participate in GD pathogenesis [ 4 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Increased Circulating Th17 but Decreased CD4⁺Foxp3⁺ Treg and CD19⁺CD1d^hiCD5⁺ Breg Subsets in New-Onset Graves’ Disease

Qin

Zhou

Fan

et al. 2017

BioMed Research International

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Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves' disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4+IL-17+ Th17, CD4+Foxp3+ Tregs, and CD19+CD1dhiCD5+ Bregs and meanwhile, for real-time PCR measurement of gene expressions of RORγt, IL-17 and IL-10. The proportions of Tregs and Bregs as well as the Foxp3 gene expression but not IL-10 were significantly decreased in GD group compared with the healthy controls. The frequency of Th17 together with the gene expressions of RORγt and IL-17 were significantly increased in the GD group. Furthermore, the Th17/Treg ratio was also significantly higher in GD group. A significant positive correlation between Th17 and TSAb (r = 0.656, p < 0.001) but significant negative correlations between Treg/Breg and TSAb (r = −0.339, p = 0.032; r = −0.759, p < 0.001) were identified among the participants. This study indicated that increased Th17 and impaired Treg responses, along with a decreased number of CD19+CD1dhiCD5+ Breg cells, were involved in GD pathogenesis.

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“…The analysis of Th17/Treg T cell proportions in peripheral blood from patients with Graves' disease revealed significantly lower ratios of CD4 + IL17 + / CD4 + CD25 + CD127 -(p < 0.0021) and CD4 + IL17 + /CD4 + CD25 + CD127 -FoxP3 + (p < 0.0031) than in the control group [27]. In addition, the number of CD4 + CD25 + Foxp3 + T lymphocyte was also significantly reduced in the autoantigen thyroid-stimulating hormone receptor-immunized mice [28].…”

Section: Discussionmentioning

confidence: 93%

Decreased Frequencies of Peripheral Blood CD4+CD25+CD127–Foxp3+ in Patients with Graves’ Disease and Graves’ Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells

et al. 2017

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Graves' orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves' disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127, Foxp3) on T cells and their ability to respond to IGF-1 stimulation. In patients with GD without GO, we found lowered percentages of CD4 Foxp3 cells, as compared to nodular goiter 1.77 vs. 5.42% (p=0.0276). Similarly, significantly reduced frequencies of CD4CD25CD127Foxp3 and CD4CD25CD127 cells were observed in GD patients as compared to nodular goiter patients with hyperthyreosis, (0.7 vs. 1.48%) (p=0.0071) and (14.5 vs. 37.2%) (p=0.0051), respectively. In GO with active GO, only the percentage of CD4CD25CD127 cells was found to be decreased versus nodular goiter (9.35 vs. 37.2) (p=0.0275). Stimulation of PBMC derived from GO patients with IGF-1 resulted in significant increase of frequency of both CD4 Foxp3 and CD4CD25CD127 Foxp3 cells. Decreased frequencies of peripheral blood CD4CD25CD127Foxp3 in patients with GD and GO could be an useful marker of autoimmune process and perhaps a possible target for future therapies. This is the first study demonstrating Treg-enhancing effects of IGF-1. Thus IGF-1 can be accounted for modulating Treg cell-related action in GO.

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Regulatory T cells but not T helper 17 cells are modulated in an animal model of Graves’ hyperthyroidism

Cited by 32 publications

References 26 publications

Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease

Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease

Increased Circulating Th17 but Decreased CD4⁺Foxp3⁺ Treg and CD19⁺CD1d^hiCD5⁺ Breg Subsets in New-Onset Graves’ Disease

Decreased Frequencies of Peripheral Blood CD4+CD25+CD127–Foxp3+ in Patients with Graves’ Disease and Graves’ Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells

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Regulatory T cells but not T helper 17 cells are modulated in an animal model of Graves’ hyperthyroidism

Cited by 32 publications

References 26 publications

Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease

Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease

Increased Circulating Th17 but Decreased CD4+Foxp3+ Treg and CD19+CD1dhiCD5+ Breg Subsets in New-Onset Graves’ Disease

Decreased Frequencies of Peripheral Blood CD4+CD25+CD127–Foxp3+ in Patients with Graves’ Disease and Graves’ Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells

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Increased Circulating Th17 but Decreased CD4⁺Foxp3⁺ Treg and CD19⁺CD1d^hiCD5⁺ Breg Subsets in New-Onset Graves’ Disease