ArticleImmunologic research2015
Elevated follicular helper T cells and expression of IL-21 in thyroid tissues are involved in the pathogenesis of Graves' disease.
Article in Immunologic research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Aberrant STAT3 activation and overproduction of IL-21 in systemic lupus erythematosus: role of miR-155 and miR-21 in target genesFrontiers in immunology · 2026Article
- Characterizing the Interplay of Lymphocytes in Graves' Disease.International journal of molecular sciences · 2023Review
- MiR-29a-3p negatively regulates circulating Tfh memory cells in patients with Graves' disease by targeting ICOS.Immunologic research · 2023Article
- Identification of optimal feature genes in patients with thyroid associated ophthalmopathy and their relationship with immune infiltration: a bioinformatics analysis.Frontiers in endocrinology · 2023Article
- Retrospective analysis of low-dose interleukin-2 therapy on chronic autoimmune thyroid disease with concurrent systemic lupus erythematosus.Annals of medicine · 2023Article
- Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases.Frontiers in immunology · 2022Review
- Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves' Disease.Frontiers in cell and developmental biology · 2021Review
- Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis.Journal of immunology research · 2021Review
- Tissue Infiltrating LTi-Like Group 3 Innate Lymphoid Cells and T Follicular Helper Cells in Graves' and Hashimoto's Thyroiditis.Frontiers in immunology · 2020Article
- The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition.International journal of molecular sciences · 2019Review
- Increased Human Interleukin-32 Expression Is Related to Disease Activity of Graves' Disease.Frontiers in endocrinology · 2019Article
- Constitutive Changes in Circulating Follicular Helper T Cells and Their Subsets in Patients with Graves' Disease.Journal of immunology research · 2018Article
- T Follicular Helper Cells in Autoimmune Disorders.Frontiers in immunology · 2018Review
- The Role of Integrin Expressing Cells in Modulating Disease Susceptibility and Progression (January 2016).International trends in immunity · 2016Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The follicular helper T cell (Tfh) and IL-21 have been shown to play an important role in many autoimmune diseases. However, less is known about their role in Graves' disease (GD). This study aimed to investigate the expression of Tfhs and related factors (IL-21, IL-21R, CXCR5, and CXCL13) in GD thyroid tissues and to explore the effect of IL-21 on thyroid follicular cells (TFCs). The expression of Tfh-related factors in GD and normal thyroid tissues was validated using immunohistochemistry, real-time polymerase chain reaction and Western blotting. Confocal microscopy confirmed the presence of Tfh and IL-21R on CD4(+)T-/CD19(+)B cell in GD thyroid tissues. Furthermore, the effect of IL-21 on cAMP production in TFCs upon thyroid-stimulating antibody (TSAb) stimulation was also examined by an in vitro bioassay. The increased expression of Tfh-related factors was observed in GD thyroid tissues compared to control subjects. Confocal microscopy further confirmed the presence of Tfhs and the expression of IL-21R on CD4(+)T cells and CD19(+)B cells in GD thyroid tissues. Moreover, the expression of IL-21mRNA in GD thyroid tissues was correlated with the levels of thyroid autoantibodies. Additionally, IL-21 could indirectly promote cAMP production upon TSAb stimulation in TFCs when cooperating with lymphocytes, and GD TFCs were more sensitive to IL-21 stimulation than normal TFCs. There is increased expression of Tfhs and related factors (IL-21, IL-21R, CXCR5, and CXCL13) in GD thyroid tissues, and the expression of IL-21mRNA in GD thyroid tissues was found to correlate with the serum levels of thyroid autoantibodies and thyroid hormones. Moreover, IL-21 could indirectly enhance the biological activity of TFCs upon TSAb stimulation when cooperating with lymphocytes in vitro, particularly in GD TFCs, suggesting that Tfh and IL-21 might be involved in the pathogenesis of GD.
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