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Mediators of Inflammation 2023To investigate whether the Notch signaling pathway participates in the occurrence and development of experimental autoimmune thyroiditis (EAT) by affecting the...
PURPOSE
To investigate whether the Notch signaling pathway participates in the occurrence and development of experimental autoimmune thyroiditis (EAT) by affecting the differentiation and function of Th17 cells.
MATERIALS AND METHODS
Experimental mice were randomly divided into a control group, an EAT-A group (porcine thyroid immunoglobulin- (pTg-) treated mice) and an EAT-B group (treated with the DAPT -secretase inhibitor before pTg). HE staining, IHC staining, flow cytometry, RT-qPCR, and ELISA were used to evaluate the degrees of thyroiditis, detect the percentage of Th17 cells and measure the expression of retinoic acid-related orphan receptor gamma t (RORt), interleukin-17A (IL-17A), and the main components of the Notch signaling pathway.
RESULTS
The degrees of thyroiditis, the proportions of Th17 cells, and the expression of RORt and IL-17A were significantly decreased in the EAT-B group after blocking the Notch signaling pathway by DAPT, and these parameters were significantly increased in the EAT-A group compared to the control group (all < 0.05). Additionally, the Th17 cell percentages and IL-17A concentrations in spleen mononuclear cells (SMCs) from EAT-A mice decreased in a dose-dependent manner after DAPT treatment in vitro (all < 0.01). Correlation analyses revealed that the Th17 cell percentages were positively correlated with the serum TgAb titers, Notch pathway-related mRNA expression levels, and IL-17A concentrations in EAT mice (all < 0.05).
CONCLUSIONS
The expression of Notch signaling pathway components was upregulated in EAT mice, but blockade of the Notch signaling pathway alleviated the degree of thyroiditis, decreased the Th17 cell proportions, and downregulated the IL-17A effector cytokine both in vivo and in vitro. These findings suggested that the Notch signaling pathway may be involved in the pathogenesis of thyroid autoimmune injury in EAT mice by promoting the differentiation of Th17 cells.
Topics: Mice; Animals; Thyroiditis, Autoimmune; Interleukin-17; Th17 Cells; Nuclear Receptor Subfamily 1, Group F, Member 3; Platelet Aggregation Inhibitors; Hashimoto Disease; Cell Differentiation; Signal Transduction
PubMed: 36643586
DOI: 10.1155/2023/1195149 -
Best Practice & Research. Clinical... Mar 2023Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid... (Review)
Review
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid diseases (AITD). The pathogenesis involves a complex interplay between environment and genes. Specific susceptibility genes have been discovered that predispose to AITD, including thyroid-specific and immune-regulatory genes. Growing evidence has revealed that genetic and epigenetic variants can alter autoantigen presentation during the development of immune tolerance, can enhance self-peptide binding to MHC (major histocompatibility complex), and can amplify stimulation of T- and B-cells. These gene-driven mechanistic discoveries lay the groundwork for novel treatment targets. This review summarizes recent advances in our understanding of key AITD susceptibility genes (Tg, TSHR, HLA-DR3, and CD40) and their translational therapeutic potential.
Topics: Humans; Genetic Predisposition to Disease; Hashimoto Disease; Autoimmune Diseases; Graves Disease; Epigenesis, Genetic; Thyroid Diseases
PubMed: 35459628
DOI: 10.1016/j.beem.2022.101661 -
Best Practice & Research. Clinical... Mar 2023MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. They are emerging as potential biomarkers and as therapeutic... (Review)
Review
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. They are emerging as potential biomarkers and as therapeutic targets for several diseases including autoimmune thyroid diseases (AITD). They control a wide range of biological phenomena, including immune activation, apoptosis, differentiation and development, proliferation and metabolism. This function makes miRNAs attractive as disease biomarker candidates or even as therapeutic agents. Because of their stability and reproducibility circulating miRNAs have been an interesting area of research in many diseases, and studies describing their role in the immune response and in autoimmune diseases have progressively developed. The mechanisms underlying AITD remain elusive. AITD pathogenesis is characterized by a multifactorial interplay based on the synergy between susceptibility genes and environmental stimulation, together with epigenetic modulation. Understanding the regulatory role of miRNAs could lead to identify potential susceptibility pathways, diagnostic biomarkers and therapeutic targets for this disease. Herein we update our present knowledge on the role of microRNAs in AITD and discuss on their importance as possible diagnostic and prognostic biomarkers in the most prevalent AITDs: Hashimoto's thyroiditis (HT), Graves' disease (GD) and Graves' Ophthalmopathy (GO). This review provides an overview of the state of the art in the pathological roles of microRNAs as well as in possible novel miRNA-based therapeutic approaches in AITD.
Topics: Humans; MicroRNAs; Reproducibility of Results; Genetic Predisposition to Disease; Hashimoto Disease; Graves Disease; Autoimmune Diseases; Biomarkers; Graves Ophthalmopathy; Thyroid Diseases
PubMed: 36801129
DOI: 10.1016/j.beem.2023.101741 -
BioMed Research International 2022Autoimmune thyroid diseases (AITDs), representative autoimmune diseases, mainly consist of Graves' disease (GD) and Hashimoto's thyroiditis (HT). In this passage, we...
BACKGROUND
Autoimmune thyroid diseases (AITDs), representative autoimmune diseases, mainly consist of Graves' disease (GD) and Hashimoto's thyroiditis (HT). In this passage, we investigated the association between vascular endothelial growth factor C (VEGFC) gene polymorphisms and AITDs.
METHODS
A total of 1084 patients with AITDs and 794 healthy controls were tested for VEGFC gene genotypes in four single nucleotide polymorphisms (SNPs) by high-throughput sequencing, and the correlation between VEGFC gene polymorphisms and AITDs was statistically analyzed.
RESULTS
The genotype distribution of rs3775194 was statistically associated with AITDs compared with the control group. Rs3775194 was associated with AITDs under the overdominant model, both before and after adjusting for confounding factors, while the other three SNPs were not associated with GD and HT. There was a prominent discrepancy between male healthy controls and male AITD patients under overdominant model in rs3775194 and the recessive model in rs11947611. The genotype distribution of rs3775194 was statistically related to male HT.
CONCLUSION
These results reveal the correlation between VEGFC mutation and AITD susceptibility.
Topics: Alleles; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Genotype; Graves Disease; Hashimoto Disease; Humans; Male; Polymorphism, Single Nucleotide; Thyroiditis, Autoimmune; Vascular Endothelial Growth Factor C
PubMed: 35865663
DOI: 10.1155/2022/2603519 -
Mayo Clinic Proceedings Oct 2010
Topics: Autoimmunity; Brain Diseases; Diagnosis, Differential; Hashimoto Disease; Humans
PubMed: 20884823
DOI: 10.4065/mcp.2010.0536 -
Frontiers in Immunology 2022Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform.
METHODS
The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed.
RESULTS
A total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto's thyroiditis (HT) and hypothyroid groups, but not in the Graves' disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found.
CONCLUSIONS
PLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022341823.
Topics: Humans; Hashimoto Disease; Mean Platelet Volume; Platelet Count; Graves Disease; Hyperthyroidism; Hypothyroidism
PubMed: 36618418
DOI: 10.3389/fimmu.2022.1089469 -
Trends in Immunology May 2023Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively.... (Review)
Review
Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.
Topics: Humans; Thyroiditis, Autoimmune; Hashimoto Disease; Graves Disease; Autoimmune Diseases
PubMed: 37061365
DOI: 10.1016/j.it.2023.03.007 -
Frontiers in Immunology 2022Autoimmune thyroiditis (AIT) is the most common autoimmune disease, affecting 3-5% patients worldwide. In recent years, approximately 200 articles on AIT have been...
BACKGROUND
Autoimmune thyroiditis (AIT) is the most common autoimmune disease, affecting 3-5% patients worldwide. In recent years, approximately 200 articles on AIT have been published annually in various journals. However, to date, no article has systematically assessed the related literature. Therefore, we conducted a bibliometric analysis on AIT to reveal the dynamic scientific developments and help researchers gain a global perspective while exploring the hotspots and development trends.
METHODS
AIT-related articles and reviews from 2000 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The following search terms were used to extract document data: TS= (" autoimmune thyroiditi*") OR TI= ("chronic lymphocytic thyroiditi*") OR TI=(hashimoto*) OR TI= ("postpartum thyroiditis"). We selected articles and reviews published in English from 2000 to 2022. Three software programs (VOSviewer, CiteSpace, Pajek) were employed to analyze the contribution and co-occurrence relationships of different references, countries/regions, institutes, journals and also keywords in this field.
RESULTS
This scientometric study included 2290 English papers published in 723 journals with 39661 co-cited references from 561 institutions in 120 countries/regions. Based on the reference and keyword analysis, researchers used to focus on "apoptosis", "insulin resistance", "encephalopathy", "IFN-γ" related to AIT during the past 20 years. However, with the development of other novel directions such as "papillary thyroid cancer" (2018-2022), "Vitamin D" (2016-2022), "oxidative stress" (2018-2022), "polymorphism" (2019-2022) and "association" (2020-2022), researchers are more interested in the relationship between papillary thyroid carcinoma and AIT, the effect of vitamin D supplementation on AIT, the oxidative stress in thyroid disease as well as the influence of polymorphism.
CONCLUSION
Bibliometric analysis of the outputs of AIT shows an overview of the current status of the research on AIT. The associations between papillary thyroid carcinoma, vitamin D, oxidative stress, polymorphism and AIT are major research frontiers. However, further research and collaboration are still required worldwide. Our findings can help researchers grasp the research status of AIT and quickly determine new directions for future research.
Topics: Bibliometrics; Biomedical Research; Female; Hashimoto Disease; Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroiditis, Autoimmune; Vitamins
PubMed: 36032148
DOI: 10.3389/fimmu.2022.953465 -
Endokrynologia Polska 2021The phenomenon of autoimmunity develops as a result of the triggering factor released by damaged cells. This leads to an infiltration of CD4+ cells involved in... (Review)
Review
The phenomenon of autoimmunity develops as a result of the triggering factor released by damaged cells. This leads to an infiltration of CD4+ cells involved in stimulating the effector cells cytotoxicity and stimulating the humoral response. One of the most common autoimmune disorders are autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves's diseases. Helper T lymphocytes, which are divided into Th1, Th2, Tregs, and the relatively new groups Th17, Th22, and Th9, are involved in the pathogenesis of AITD. CD4+ cell subtypes mature and differentiate by specific transcription factors and in a specific interleukin environment. Not only are Th1 and Th2 cells involved in the development of AITD, but also Th17, Th22, and Th9 lymphocytes and their correlation to Tregs lymphocytes. The plasticity of the CD4+ cells is very important, affecting the balance between these cells, as well the factors modulating their phenotypic variability. Patients with AITD have an increased percentage of Th17, Th22, and Th9 cells as well as defective function of Tregs lymphocytes. The balance between Th17 cells (and also other cytotoxic T cells) and Treg cells is also very important. Understanding the role of CD4 cells in the pathogenesis of AITD may be important not only for the development of the knowledge, but also for determining therapeutic targets.
Topics: Autoimmune Diseases; CD4-Positive T-Lymphocytes; Graves Disease; Hashimoto Disease; Humans; T-Lymphocytes, Helper-Inducer
PubMed: 34647609
DOI: 10.5603/EP.a2021.0076 -
International Journal of Molecular... Mar 2023Strategies concerning thyroid anomalies in patients confirmed with psoriasis, either on clinical level or molecular levels, and their genetic findings remain an open... (Review)
Review
Strategies concerning thyroid anomalies in patients confirmed with psoriasis, either on clinical level or molecular levels, and their genetic findings remain an open issue. Identification of the exact subgroup of individuals that are candidates to endocrine assessments is also controversial. Our purpose in this work was to overview clinical and pathogenic data concerning psoriasis and thyroid comorbidities from a dual perspective (dermatologic and endocrine). This was a narrative review of English literature between January 2016 and January 2023. We included clinically relevant, original articles with different levels of statistical evidence published on PubMed. We followed four clusters of conditions: thyroid dysfunction, autoimmunity, thyroid cancer, and subacute thyroiditis. A new piece of information in this field was the fact that psoriasis and autoimmune thyroid diseases (ATD) have been shown to be related to the immune-based side effects of modern anticancer drugs-namely, immune checkpoint inhibitors (ICP). Overall, we identified 16 confirmatory studies, but with heterogeneous data. Psoriatic arthritis had a higher risk of positive antithyroperoxidase antibodies (TPOAb) (25%) compared to cutaneous psoriasis or control. There was an increased risk of thyroid dysfunction versus control, and hypothyroidism was the most frequent type of dysfunction (subclinical rather than clinical), among thyroid anomalies correlated with >2-year disease duration, peripheral > axial and polyarticular involvement. With a few exceptions, there was a female predominance. Hormonal imbalance included, most frequently, low thyroxine (T4) and/or triiodothyronine (T3) with normal thyroid stimulating hormone (TSH), followed by high TSH (only one study had higher total T3). The highest ratio of thyroid involvement concerning dermatologic subtypes was 59% for erythrodermic psoriasis. Most studies found no correlation between thyroid anomalies and psoriasis severity. Statistically significant odds ratios were as follows: hypothyroidism: 1.34-1.38; hyperthyroidism: 1.17-1.32 (fewer studies than hypo); ATD: 1.42-2.05; Hashimoto's thyroiditis (HT): 1.47-2.09; Graves' disease: 1.26-1.38 (fewer studies than HT). A total of 8 studies had inconsistent or no correlations, while the lowest rate of thyroid involvement was 8% (uncontrolled studies). Other data included 3 studies on patients with ATD looking for psoriasis, as well as 1 study on psoriasis and thyroid cancer. ICP was shown to potentially exacerbate prior ATD and psoriasis or to induce them both de novo (5 studies). At the case report level, data showed subacute thyroiditis due to biological medication (ustekinumab, adalimumab, infliximab). Thyroid involvement in patients with psoriasis thus remained puzzling. We observed significant data that confirmed a higher risk of identifying positive antibodies and/or thyroid dysfunction, especially hypothyroidism, in these subjects. Awareness will be necessary to improve overall outcomes. The exact profile of individuals diagnosed with psoriasis who should be screened by the endocrinology team is still a matter of debate, in terms of dermatological subtype, disease duration, activity, and other synchronous (especially autoimmune) conditions.
Topics: Humans; Female; Male; Thyroiditis, Autoimmune; Thyroiditis, Subacute; Hypothyroidism; Thyroid Diseases; Hashimoto Disease; Graves Disease; Thyrotropin; Thyroid Neoplasms; Psoriasis
PubMed: 36902323
DOI: 10.3390/ijms24054894