Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases

Zaķe, Tatjana; Skuja, Sandra; Kalere, Ieva; Konrāde, Ilze; Groma, Valērija

doi:10.1097/md.0000000000011211

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…Similarly, IL-17 levels in the peripheral blood and thyroid tissues did not differ significantly between adult patients with GD and controls (Qin Q et al, 2012). An increased expression of IL-17 within thyroid tissues from HT and GD patients was found also in our study (Zake et al, 2018). We observed stronger immunoexpression level of IL-17A in thyroid follicular cells in HT and GD patients when compared to patients with colloid goiter, thus suggesting that Th17 cells had an essential role in AITD pathogenesis (p < 0.001 and p = 0.007, respectively) (Fig.…”

Section: Th17 Cells and Thyroid Autoimmunitysupporting

confidence: 84%

Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

Zaķe

Skuja

Lejnieks

et al. 2019

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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Autoimmune thyroid diseases (AITD) mainly include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.

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Section: Th17 Cells and Thyroid Autoimmunitysupporting

confidence: 84%

Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

Zaķe

Skuja

Lejnieks

et al. 2019

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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“…Several studies have demonstrated a significant increase of Th17 lymphocytes and IL-17 in the peripheral blood and/or thyroid tissues of AITD patients, suggesting their contributions to thyroid autoimmunity. The overexpression of IL-17 within thyroid tissues from HT and GD patients compared to controls was also revealed in our previous study [17]. However, the role of interleukins in promoting the differentiation of Th17 cells has not been thoroughly evaluated in HT and GD pathogenesis.…”

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confidence: 53%

Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1β in Hashimoto’s thyroiditis but not in Graves’ disease

et al. 2019

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T helper (Th) 17 cells and interleukin (IL)-17 play a significant role in the pathogenesis of autoimmune thyroid disease (AITD). However, it has recently become clear that Th17 cells are more heterogeneous and exhibit two different phenotypes, whereas IL-23 and IL-1β are crucial for the generation of pathogenic Th17 lymphocytes. We aimed to investigate the association between IL-17 and Th17-promoting cytokines in AITD by studying the immunoexpression patterns of IL-17, IL-23, and IL-1β in thyroid tissue. Following thyroidectomy, 29 patients with AITD (21 cases of Hashimoto's thyroiditis (HT) and 8 cases of Graves' disease (GD)) and 18 patients with colloid goiter, as controls, were enrolled in this study, and immunohistochemistry was performed. The expression level of IL-17 in thyrocytes was significantly higher in HT and GD patients than in colloid goiter patients. Immunopositivity for both IL-23 and IL-1β was significantly increased in HT patients compared to GD and colloid goiter patients. However, no difference was found between IL-23 or IL-1β expression in patients with GD and colloid goiter. A positive correlation between IL-17 and IL-23 as well as IL-17 and IL-1β expression was observed in HT patients (r = 0.574, p = 0.007 and r = 0.461, p = 0.036, respectively). In the GD group, IL-17 was positively correlated with IL-1β (r = 0.817, p = 0.013) but not with IL-23 expression. We found increased IL-23 and IL-1β expression in the HT group but not in the GD group. Furthermore, both interleukins were correlated with IL-17 immunopositivity in thyroid tissue, suggesting that pathogenic Th17-promoting cytokines may play a role in HT pathogenesis.

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“…In terms of thyroid cell injury, cytokines derived from the lymphocytic infiltrate play a key role, including their ability to stimulate the thyroid cells themselves to release proinflammatory mediators, thus amplifying and perpetuating the autoimmune response [ 3 ]. Previous studies have shown that blood and thyroid Th17 cells which secrete the cytokine IL-17 are increased in HT, as in many other autoimmune disorders, but a recent study has reported finding an additional source of IL-17 in the thyroid follicular cells themselves in HT [ 31 ]. Expression correlated with the appearance of CD68 + macrophages inside the follicle although there was no evidence to support a direct role of IL-17 in tight junction dysfunction.…”

Section: Pathogenetic Mechanismsmentioning

confidence: 99%

An update on the pathogenesis of Hashimoto’s thyroiditis

Weetman

2020

J Endocrinol Invest

119

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It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto’s thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tolerance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT.

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Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases

Cited by 13 publications

References 35 publications

Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1β in Hashimoto’s thyroiditis but not in Graves’ disease

An update on the pathogenesis of Hashimoto’s thyroiditis

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