Association of increased eomesodermin, BCL6, and granzyme B expression with major clinical manifestations of Hashimoto’s thyroiditis – an observational study

Štefanić, Mario; Tokić, Stana; Stević, Mirjana Suver; Glavaš‐Obrovac, Ljubica

doi:10.1080/08820139.2018.1423571

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…CD4 + T cells are also known to show cytotoxic phenotypes in some conditions, including chronic viral infections (13,14), and some tumors, including malignant melanoma (15) and multiple myeloma (16). It has been reported that cytotoxic CD4 + T cells expressing perforin (a cytotoxic molecule) infiltrated into thyroid glands in patients with Hashimoto thyroiditis (17), and that the expression of another cytotoxic molecule, granzyme B, in peripheral T cells was higher in patients with Hashimoto thyroiditis than in T cells isolated from healthy controls (18). However, it remains unclear if CD4 + T cells are present in the involved organs in irAE or if they exhibit any cytotoxic characteristics.…”

Section: Introductionmentioning

confidence: 99%

CD4 ⁺ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

et al. 2021

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Immune-related adverse events induced by anti–programmed cell death–1 antibodies (PD-1-Ab), including destructive thyroiditis (thyroid-irAE), are thought to be caused by activated T cells. However, the T cell subsets that are directly responsible for damaging self-organs remain unclear. To clarify which T cell subsets are involved in the development of thyroid-irAE, a mouse model of thyroid-irAE was analyzed. PD-1-Ab administration 2.5 months after immunization with thyroglobulin caused destructive thyroiditis. Thyroiditis was completely prevented by previous depletion of CD4+ T cells and partially prevented by depleting CD8+ T cells. The frequencies of central and effector memory CD4+ T cell subsets and the secretion of interferon-γ after stimulation with thyroglobulin were increased in the cervical lymph nodes of mice with thyroid-irAE compared with controls. Histopathological analysis revealed infiltration of CD4+ T cells expressing granzyme B in thyroid glands and major histocompatibility complex class II expression on thyrocytes in mice with thyroid-irAE. Adoptive transfer of CD4+ T cells from cervical lymph nodes in mice with thyroid-irAE caused destruction of thyroid follicular architecture in the irradiated recipient mice. Flow cytometric analyses showed that the frequencies of central and effector memory CD4+ T cells expressing the cytotoxic marker CD27 were higher in peripheral blood mononuclear cells collected from patients with thyroid-irAE induced by PD-1-Ab versus those without. These data suggest a critical role for cytotoxic memory CD4+ T cells activated by PD-1-Ab in the pathogenesis of thyroid-irAE.

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Section: Introductionmentioning

confidence: 99%

CD4 ⁺ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

et al. 2021

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“…The main pathological features include lymphocytic infiltration in germinal centers, diffuse enlargement of the thyroid gland, destruction and atrophy of thyrocytes, and interstitial fibrosis. The serological feature is persistent positivity of thyroid autoantibodies including thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) 4, 5. The pathogenesis of HT depends on many elements, including genetic predisposition, environmental implication, and immunological factors.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA Expression Profiling and the Potential Role of hsa_circ_0089172 in Hashimoto’s Thyroiditis via Sponging miR125a-3p

Xiong

Peng

Ding

et al. 2019

Molecular Therapy - Nucleic Acids

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Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs), but the role of circRNAs in Hashimoto's thyroiditis (HT) has not been defined. In this study, peripheral blood samples from five patients with HT and five healthy volunteers were investigated by Illumina HiSeq Sequencer. A total of 627 differentially expressed circRNAs including 370 upregulated and 257 downregulated ones were identified in HT patients. Four upregulated circRNAs indicated the same rising tendency toward sequencing results. The expression of hsa_circ_0089172 was upregulated and correlated positively with the serum level of the thyroid peroxidase antibody. Two perfectly matched binding sites of miR-125a-3p were found in hsa_circ_0089172 sequences with bioinformatics tools. The expression of miR-125a-3p was decreased in the HT patients and correlated inversely with an elevated level of hsa_circ_0089172. Moreover, knockdown of hsa_circ_0089172 resulted in an increase of the expression of miR-125a-3p in vitro. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0089172 had significant value in HT diagnosis. Taken together, these results demonstrate that hsa_circ_0089172 as a potential diagnostic biomarker of HT and may play a crucial role in the pathogenesis of HT via sponging miR-125a-3p.

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“…Some previous papers revealed that decidual CD8 + T cells of healthy pregnant women do not express GZMB and PRF1 ( 80 , 81 ). However, GZMB was overrepresented in peripheral blood T cells from HT patients and its levels varied by age, thyroid volume, and disease severity ( 82 ). Elevated GZMB in preeclampsia inhibits invasion and migration of trophoblasts ( 83 ).…”

Section: Discussionmentioning

confidence: 99%

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

Xie

et al. 2023

Front. Endocrinol.

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ObjectiveAutoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI).MethodsWe collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis.ResultsWe characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+GZMK+, T CD8+ Cytotoxic and ILC3 CD3E- cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased.ConclusionImmune imbalance exists in endometrium during WOI, which may impact embryo implantation.

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Association of increased eomesodermin, BCL6, and granzyme B expression with major clinical manifestations of Hashimoto’s thyroiditis – an observational study

Abstract: Our exploratory results suggest a role for GZMB, EOMES, and BCL6 in the context of HT, thyroid injury, and aggressive/advanced disease forms. Functions enriched within differentially expressed transcripts could be an important new target in understanding the pathogenesis of HT.

Cited by 7 publications

References 49 publications

CD4 ⁺ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

CD4 ⁺ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

Circular RNA Expression Profiling and the Potential Role of hsa_circ_0089172 in Hashimoto’s Thyroiditis via Sponging miR125a-3p

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

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Association of increased eomesodermin, BCL6, and granzyme B expression with major clinical manifestations of Hashimoto’s thyroiditis – an observational study

Abstract: Our exploratory results suggest a role for GZMB, EOMES, and BCL6 in the context of HT, thyroid injury, and aggressive/advanced disease forms. Functions enriched within differentially expressed transcripts could be an important new target in understanding the pathogenesis of HT.

Cited by 7 publications

References 49 publications

CD4 + T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

CD4 + T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

Circular RNA Expression Profiling and the Potential Role of hsa_circ_0089172 in Hashimoto’s Thyroiditis via Sponging miR125a-3p

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

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CD4 ⁺ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

CD4 ⁺ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice