The Frequency of Intrathyroidal Follicular Helper T Cells Varies with the Progression of Graves’ Disease and Hashimoto’s Thyroiditis

Cai, Yun; Wang, Zhixiao; Liu, Xiaoyun; Wei, Ling; Li, Shushu; Zheng, Xuqin; Yang, Tao; Xu, Xinyu

doi:10.1155/2022/4075522

Cited by 9 publications

(9 citation statements)

References 36 publications

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“…They have been shown to be involved in the pathogenesis of many autoimmune diseases because the dysregulation of Tfh cell activity results in the increased production in antibodies against self-antigens. In a study conducted by Cai et al, an increased number in Tfh lymphocytes were found in the thyroid glands of patients with HT, which increased with the progression of the disease [37]. A correlation was also found between the number of these cells in the blood and thyroid and the level of antithyroid antibodies, especially anti-TG antibodies and free triiodothyronine.…”

Section: The Involvement Of Tfh In the Pathogenesis Of Hashimoto's Th...mentioning

confidence: 87%

“…Patients with chronic lymphocytic thyroiditis also show an increase in the number of Tfh belonging to the CD4+ T cell group, which play an important role in the immune response by producing IL-21 and stimulating B-lymphocyte activity [37]. They have been shown to be involved in the pathogenesis of many autoimmune diseases because the dysregulation of Tfh cell activity results in the increased production in antibodies against self-antigens.…”

Section: The Involvement Of Tfh In the Pathogenesis Of Hashimoto's Th...mentioning

confidence: 99%

“…A correlation was also found between the number of these cells in the blood and thyroid and the level of antithyroid antibodies, especially anti-TG antibodies and free triiodothyronine. It has been suggested that, due to their importance in the development of autoimmune thyroid diseases, Tfh lymphocytes may serve as markers indicating the presence of these diseases and allowing for the assessment of their progression [37].…”

Section: The Involvement Of Tfh In the Pathogenesis Of Hashimoto's Th...mentioning

confidence: 99%

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The Role of the Immune System in the Course of Hashimoto’s Thyroiditis: The Current State of Knowledge

Wrońska,

Hałasa,

Szczuko

2024

IJMS

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The process of thyroid autoimmunization develops against the background of genetic predispositions associated with class II human leukocyte antigens (HLA-DR), as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and forkhead transcription box protein P3 (FOXP3). Environmental factors, such as vitamin D deficiency, Zn, Se, and Mg, as well as infections, chronic stress, pregnancy, smoking, alcohol, medications, intestinal dysbiosis, and malnutrition, also play an important role. The first stage of autoimmunization involves the accumulation of macrophages and dendritic cells, as well as plasma cells. In the second stage, the mutual interactions of individual cells in the immune system lead to a decrease in the level of CD8+ in favor of CD4+, which intensifies the synthesis of T lymphocyte derivatives, especially Th1, Th17, Tfh, and Tc, reducing the level of Treg. Consequently, the number of the anti-inflammatory cytokines IL10 and IL2 decreases, and the synthesis of the pro-inflammatory cytokines IL-2, Il-12, Il-17, IL-21, IL-22, IFN-γ, and TNF-α increases. The latter two especially trigger the pyroptosis process involving the inflammasome. Activation of the inflammasome by IL-β and IL-18 produced by macrophages is one of the mechanisms of pyroptosis in the course of Hashimoto’s thyroiditis, involving Gram-negative bacteria and NLRC4. In the next step, the apoptosis of thyroid cells is initiated by the intensification of perforin, granzyme, and proteoglycan synthesis by Tc and NK cells. The current findings raise many possibilities regarding interventions related to the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines produced by both T and B lymphocytes. Furthermore, since there is currently no effective method for treating thyroid autoimmunity, a summary of the review may provide answers regarding the treatment of not only Hashimoto’s thyroiditis, but also other autoimmune diseases associated with autoimmunity.

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Section: The Involvement Of Tfh In the Pathogenesis Of Hashimoto's Th...mentioning

confidence: 87%

Section: The Involvement Of Tfh In the Pathogenesis Of Hashimoto's Th...mentioning

confidence: 99%

Section: The Involvement Of Tfh In the Pathogenesis Of Hashimoto's Th...mentioning

confidence: 99%

See 1 more Smart Citation

The Role of the Immune System in the Course of Hashimoto’s Thyroiditis: The Current State of Knowledge

Wrońska,

Hałasa,

Szczuko

2024

IJMS

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“…These researchers hypothesize that the thyroid hormones T3 and T4 may encourage T cell proliferation and the decrease in hormones after treatment correlates to the observed decrease in Tfh cells [ 32 ]. One study, however, had different findings, concluding that there was no significant difference in Tfh cells in the PB and that they did not correlate with thyroid hormone levels [ 57 ].…”

Section: T Cellsmentioning

confidence: 99%

“…IL-21 has been found to be elevated in the serum of GD patients and is strongly correlated with TSAb in untreated patients [ 52 , 59 ]. Tfh cells marked by PD-1 or ICOS are higher in the thyroid tissue than in the PB in GD patients [ 57 ].…”

Section: T Cellsmentioning

confidence: 99%

Characterizing the Interplay of Lymphocytes in Graves’ Disease

Hansen

Johnson

Weber

et al. 2023

IJMS

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Graves’ disease (GD) is a thyroid-specific autoimmune disease with a high prevalence worldwide. The disease is primarily mediated by B cells, which produce autoantibodies against the thyroid-stimulating hormone receptor (TSHR), chronically stimulating it and leading to high levels of thyroid hormones in the body. Interest in characterizing the immune response in GD has motivated many phenotyping studies. The immunophenotype of the cells involved and the interplay between them and their secreted factors are crucial to understanding disease progression and future treatment options. T cell populations are markedly distinct, including increased levels of Th17 and follicular helper T cells (Tfh), while Treg cells appear to be impaired. Some B cells subsets are autoreactive, and anti-TSHR antibodies are the key disease-causing outcome of this interplay. Though some consensus across phenotyping studies will be discussed here, there are also complexities that are yet to be resolved. A better understanding of the immunophenotype of Graves’ disease can lead to improved treatment strategies and novel drug targets.

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Analysis of T follicular and T peripheral helper lymphocytes in autoimmune thyroid disease

Sánchez-Gutiérrez,

Martínez-Hernández,

Serrano-Somavilla

et al. 2024

Endocrine

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Purpose Peripheral helper T (Tph) cells have an important role in the induction of humoral immune responses and autoantibody production. Accordingly, it is feasible that this lymphocyte subset has a relevant role in the pathogenesis of autoimmune thyroid diseases (AITD). In this study we aim to analyze the levels and function of Tph cells in blood samples from patients with AITD. Methods We performed an observational study with cases and controls. Blood samples were obtained from nineteen patients with Hashimoto’s thyroiditis (HT), twenty-four with Graves’ disease (GD), and fifteen healthy controls. In addition, the levels of follicular T helper (Tfh) cells and Tph cells, the release of interleukin-21 (IL-21) by these lymphocytes and the number of plasmablasts were analyzed by multi-parametric flow cytometry analyses. Results Increased percentages of Tfh and Tph lymphocytes were detected in patients with HT and GD. Furthermore, an enhanced synthesis of the cytokine IL-21 by these cells was observed. Accordingly, we detected significant higher percentages of plasmablasts in patients with GD, and these values tended to be also higher in HT patients. Moreover, significant positive associations were observed between the levels of Tfh or Tph and the number of plasmablast or anti-TSHR Ab titers in patients with AITD. Conclusion Our data suggest that Tph lymphocytes may have a relevant role in the pathogenesis of AITD.

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The Frequency of Intrathyroidal Follicular Helper T Cells Varies with the Progression of Graves’ Disease and Hashimoto’s Thyroiditis

Cited by 9 publications

References 36 publications

The Role of the Immune System in the Course of Hashimoto’s Thyroiditis: The Current State of Knowledge

The Role of the Immune System in the Course of Hashimoto’s Thyroiditis: The Current State of Knowledge

Characterizing the Interplay of Lymphocytes in Graves’ Disease

Analysis of T follicular and T peripheral helper lymphocytes in autoimmune thyroid disease

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