scholarly journals Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto’s Thyroiditis

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Xiao ◽  
Jianqing Liang ◽  
Sunqiang Liu ◽  
Qiongyue Zhang ◽  
Famin Xie ◽  
...  

Hashimoto’s thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone’s understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

Author(s):  
Nadia Khessairi ◽  
Ibtissem Oueslati ◽  
Ons Rjeb ◽  
Fatma Chaker ◽  
Meriem Yazidi ◽  
...  

2020 ◽  
Vol 186 ◽  
pp. 109538
Author(s):  
Aleksandar Stojsavljević ◽  
Branislav Rovčanin ◽  
Jovana Jagodić ◽  
Danijela Drašković Radojković ◽  
Ivan Paunović ◽  
...  

1996 ◽  
Vol 74 (5) ◽  
pp. 275-278 ◽  
Author(s):  
H. Kawai ◽  
T. Mitsui ◽  
K. Yokoi ◽  
M. Akaike ◽  
K. Hirose ◽  
...  

Autoimmunity ◽  
1995 ◽  
Vol 20 (4) ◽  
pp. 231-236 ◽  
Author(s):  
T. Kotani ◽  
Y. Aratake ◽  
K. Hirai ◽  
Y. Fukazawa ◽  
H. Sato ◽  
...  

2004 ◽  
pp. 587-594 ◽  
Author(s):  
N Koriyama ◽  
M Nakazaki ◽  
H Hashiguchi ◽  
K Aso ◽  
Y Ikeda ◽  
...  

OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.


1994 ◽  
Vol 141 (2) ◽  
pp. 309-315 ◽  
Author(s):  
R Paschke ◽  
F Schuppert ◽  
M Taton ◽  
T Velu

Abstract Cytokines are thought to mediate the initiation and perpetuation of autoimmune thyroiditis. However, this concept is mainly based on in vitro findings and to date only interleukin (IL)-6 and interferon-γ (IFN-γ) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effects on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis. RNA was extracted by cesium chloride gradient centrifugation from the thyroid tissue of 12 patients undergoing thyroid resection for Graves' disease and from two patients being treated for Hashimoto's thyroiditis. Two patients with parathyroid adenomas and one patient with a goiter were used as controls. RNA was also extracted from normal human thyroid epithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-γ by polymerase chain reaction. All the cytokine mRNAs were detected in the Hashimoto's thyroid glands in large quantities. Six of the 12 Graves' disease thyroid glands showed, when compared with controls, an increased accumulation of transcripts for: IFN-γ, IL-2, -4 and -10 or IL-2, -4 and IFN-γ or IL-2 and IFN-γ or IFN-γ alone, each in one case or IL-2 alone in two cases. These cytokine profiles were not representative of a Th1 or Th2 phenotype. Increased amounts of cytokine mRNA in thyroid glands from Graves' disease patients were mostly associated with high microsomal antibody titres and/or prominent intrathyroidal lymphocytic infiltration. IL-6 and/or IL-10 mRNAs were detectable in all Graves' disease thyroid glands and in control thyroid tissue. IL-10 mRNA was not detectable in normal human thyroid epithelial cells in primary culture. Graves' disease and Hashimoto's thyroiditis clearly differ with respect to the number of positive intrathyroidal cytokine mRNAs and their levels. The different cytokine patterns in Graves' disease and in Hashimoto's thyroiditis could reflect the clinical spectrum of autoimmune thyroiditis which is characterized by thyroid tissue destruction and/or thyroid autoantibody production. These data suggest that the course of autoimmune thyroiditis is regulated by the interplay of several cytokines. Journal of Endocrinology (1994) 141, 309–315


2019 ◽  
Vol 19 (7) ◽  
pp. 1012-1021 ◽  
Author(s):  
Xuan Wang ◽  
Xiaoqing Shao ◽  
Xinhao Liu ◽  
Qiu Qin ◽  
Jian Xu ◽  
...  

Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated. Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining. Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR. Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.


1990 ◽  
Vol 123 (5) ◽  
pp. 511-518 ◽  
Author(s):  
Jaeduk Noh ◽  
Noboru Hamada ◽  
Hifumi Saito ◽  
Midori Yoshimoto ◽  
Hiroyuki Iwasaki ◽  
...  

Abstract. Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.


Cytopathology ◽  
2011 ◽  
Vol 23 (6) ◽  
pp. 419-421 ◽  
Author(s):  
P. Pandey ◽  
A. Dixit ◽  
S. Bedi ◽  
K. Kapoor ◽  
N. C. Mahajan

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