scholarly journals Thyroid Autoimmunity: Exploring the Role of Th17-associated Cytokines and Pathomorphological Mechanisms Involved in the Pathogenesis of Hashimoto’s Thyroiditis and Graves’ Disease. Summary of the Doctoral Thesis

2021 ◽  
Author(s):  
◽  
Tatjana Zaķe ◽  
Keyword(s):  
Immune Response ◽  
Plasma Levels ◽  
Th17 Cells ◽  
Thyroid Autoimmunity ◽  
Selenium Supplementation ◽  
Graves Disease ◽  
Selenium Status ◽  
Newly Diagnosed ◽  
Thyroid Follicle

The prevalence and incidence of autoimmune thyroid diseases (AITD), presenting as Graves’ disease (GD) or Hashimoto’s thyroiditis (HT), has increased significantly in recent decades. It is crucial to identify immunological and pathomorphological factors involved in thyroid autoimmunity. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD. Recently, Th17 cells have been established to play a role in the pathogenesis of AITD, however, their contribution to the initiation and progression of AITD remains unclear. Furthermore, selenium deficiency can impair the differentiation of Th cells, leading to dysfunction of cellular and humoral response. The aim of this thesis was to explore the role of Th17 cells in the pathogenesis of HT and GD by the use of different morphology methods and xMAP technology, and correlating these data with the selenium status. The initial study included 29 adult patients with AITD who underwent thyroidectomy, whereas subsequent clinical research project involved 52 patients with newly diagnosed, treatment-naïve AITD, as well as 26 healthy subjects served as controls. The plasma levels of Th17-associated cytokines – interleukin (IL)-17, IL-22, IL-23, IL-6, and IL-10 and the distribution and levels of immunoexpression IL-17, IL-23, and IL-1β within thyroid tissue were measured to characterize Th17 immune response in AITD. The integrity of the thyroid follicle by studying immunoexpression of cellular tight junctions – zonula occludens-1 and claudin-1 proteins, coupled to IL-17 and CD68, was explored. In addition, the selenium status was assessed. No significant differences in the plasma levels of Th17-associated cytokines were found among the patients with AITD and control subjects. However, the expression level of IL-17 in the thyrocytes was significantly higher in the HT and GD patients than in controls, simultaneously correlating with IL-23 and IL-1β immunopositivity in the HT group. Plasma Th17-associated cytokines’ levels were positively correlated with the severity of hyperthyroidism, independent of autoantibody levels, thus suggesting their possible role in GD pathogenesis. The changes in molecules of thyrocyte junctional complexes highlighting impairment of the integrity of thyroid follicle in HT were observed, but no significant association with IL-17 was found. Although no difference in selenium levels was observed between the AITD patients and controls, the results of the given research suggest the selenium status of the Latvian patients with newly diagnosed GD or HT is at a suboptimal level. Plasma selenium levels were negatively correlated with anti-thyroperoxidase (TPO) autoantibody titres in the HT patients, thus supporting the immunomodulatory role of selenium in AITD. Moreover, HT patients with higher anti-TPO autoantibody levels had lower levels of selenium, suggesting that these patients might benefit from selenium supplementation. Essential information deepening our knowledge about thyroid autoimmunity was obtained conducting this research, however, further experimental studies exploring the role and regulatory effects of Th17-related cytokines in the pathogenesis of AITD are required. More data from clinical studies are needed for a better understanding of the relationship between selenium supplementation and immune response.

scholarly journals Thyroid Autoimmunity: Exploring the Role of Th17-associated Cytokines and Pathomorphological Mechanisms Involved in the Pathogenesis of Hashimoto’s Thyroiditis and Graves’ Disease. Doctoral Thesis

2021 ◽  
Author(s):  
◽  
Tatjana Zaķe ◽  
Keyword(s):  
Immune Response ◽  
Plasma Levels ◽  
Th17 Cells ◽  
Thyroid Autoimmunity ◽  
Selenium Supplementation ◽  
Graves Disease ◽  
Selenium Status ◽  
Newly Diagnosed ◽  
Thyroid Follicle

The prevalence and incidence of autoimmune thyroid diseases (AITD), presenting as Graves’ disease (GD) or Hashimoto’s thyroiditis (HT), has increased significantly in recent decades. It is crucial to identify immunological and pathomorphological factors involved in thyroid autoimmunity. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD. Recently, Th17 cells have been established to play a role in the pathogenesis of AITD, however, their contribution to the initiation and progression of AITD remains unclear. Furthermore, selenium deficiency can impair the differentiation of Th cells, leading to dysfunction of cellular and humoral response. The aim of this thesis was to explore the role of Th17 cells in the pathogenesis of HT and GD by the use of different morphology methods and xMAP technology, and correlating these data with the selenium status. The initial study included 29 adult patients with AITD who underwent thyroidectomy, whereas subsequent clinical research project involved 52 patients with newly diagnosed, treatment-naïve AITD, as well as 26 healthy subjects served as controls. The plasma levels of Th17-associated cytokines – interleukin (IL)-17, IL-22, IL-23, IL-6, and IL-10 and the distribution and levels of immunoexpression IL-17, IL-23, and IL-1β within thyroid tissue were measured to characterize Th17 immune response in AITD. The integrity of the thyroid follicle by studying immunoexpression of cellular tight junctions – zonula occludens-1 and claudin-1 proteins, coupled to IL-17 and CD68, was explored. In addition, the selenium status was assessed. No significant differences in the plasma levels of Th17-associated cytokines were found among the patients with AITD and control subjects. However, the expression level of IL-17 in the thyrocytes was significantly higher in the HT and GD patients than in controls, simultaneously correlating with IL-23 and IL-1β immunopositivity in the HT group. Plasma Th17-associated cytokines’ levels were positively correlated with the severity of hyperthyroidism, independent of autoantibody levels, thus suggesting their possible role in GD pathogenesis. The changes in molecules of thyrocyte junctional complexes highlighting impairment of the integrity of thyroid follicle in HT were observed, but no significant association with IL-17 was found. Although no difference in selenium levels was observed between the AITD patients and controls, the results of the given research suggest the selenium status of the Latvian patients with newly diagnosed GD or HT is at a suboptimal level. Plasma selenium levels were negatively correlated with anti-thyroperoxidase (TPO) autoantibody titres in the HT patients, thus supporting the immunomodulatory role of selenium in AITD. Moreover, HT patients with higher anti-TPO autoantibody levels had lower levels of selenium, suggesting that these patients might benefit from selenium supplementation. Essential information deepening our knowledge about thyroid autoimmunity was obtained conducting this research, however, further experimental studies exploring the role and regulatory effects of Th17-related cytokines in the pathogenesis of AITD are required. More data from clinical studies are needed for a better understanding of the relationship between selenium supplementation and immune response.

scholarly journals Selenium in Hyperthyroidism

2020 ◽  
Vol 3 (2) ◽  
pp. 24
Author(s):  
Shiela Stefani ◽  
Lukman Halim ◽  
Diyah Eka Andayani ◽  
Fiastuti Witjaksono
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Disease ◽  
Selenium Supplementation ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Hormone Synthesis ◽  
Iodothyronine Deiodinases ◽  
Endocrine Organs ◽  
The Relationship

Introduction: Thyroid gland has the highest selenium content compare with other endocrine organs. Enzyme that catalyzing thyroid hormone activation, iodothyronine deiodinases, were identified as selenocysteine-containing proteins. Selenium levels in soil and rice consumed in Indonesia were lower than in several other countries, which can increase the risk of selenium deficiency.Methods: This is an article review of the current literatures published up to November 2018 about the role of selenium in hyperthyroid.Result: Several studies have shown that selenium supplementation can be beneficial in patients with Graves disease and autoimmune thyroiditis. Selenium has an important immunomodulatory effect, but the effects of selenium supplementation in hyperthyroid has not been conclude. Data regarding selenium intake, prevalence of deficiency, and the relationship between selenium and thyroid disease in Indonesia are limited. Various studies of selenium supplementation in thyroid disease provide controversial results, so there are no guidelines that include selenium as standard therapy hyperthyroid. Selenium supplementation can enhance the restoration of biochemical euthyroidism in Graves disease and was associated with a significant decrease in the levels of thyroid peroxidase antibodies in autoimmune thyroiditis.Conclusions: Micronutrients that play a role in thyroid hormone synthesis and maintain thyroid function in addition to selenium are iodine, iron, zinc, and vitamin A. By correcting the deficit of selenium, and meeting other micronutrient requirements may provide health benefits in patient with hyperthyroid.

Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Gut Acute Graft-Versus-Host-Disease (GVHD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2968-2968
Author(s):  
Florent Malard ◽  
Céline Bossard ◽  
Jessy Arbez ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Intestinal Mucosa ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Type I ◽  
Type I Ifn ◽  
Th17 Response

Abstract Abstract 2968 Background. Acute GVHD after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. Previous studies established an important role of Th1 cells in acute GVHD pathophysiology. However, the identification of proinflammatory Th17 cells which contribute to autoimmune diseases pathophysiology, raised the issue of the role of Th17 cells in human acute GVHD. Indeed, the contribution of Th17 cells in acute GVHD was assessed in GVHD mouse models with conflicting results. In addition, the role of the PDC subset (the professional type I IFN-secreting cells), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the acute GVHD setting. This report investigated the role of Th17 cells and their interaction with PDC in gastrointestinal (GI) biopsies taken from patients with or without acute GVHD. Patients and Methods. Studies described in this report were performed in a single centre series of 21 patients who underwent allo-SCT for different hematological malignancies (n=19) and severe aplastic anemia (n=2). The median age of patients was 53 years (range, 16–69). The stem cell source was PBSCs in 19 cases (85%), CB in 2 cases and BM in one case. Ten patients received transplant from a matched-related donor, and 11 patients from a matched-unrelated donor. A reduced-intensity conditioning regimen was used in the majority of cases (n=19; 90%) Immunohistochemistry was performed on deparaffinized tissues sections using an indirect immunoperoxydase method. A quantitative evaluation of antigens expression was performed by counting the number of positive cells in the whole biopsy at 200 magnifications for each sample. Results. In this cohort, based on standard pathology criteria, 16 patients had a histologically proven gastrointestinal acute GVHD. In all cases, biopsies were taken before initiation of systemic corticosteroid therapy. The remaining 5 patients did not have histological signs of acute GVHD (and did not develop clinical signs of acute GVHD) and thus, were used as controls. In order to identify the Th17 cell population, biopsies were tested for expression of the CD161 and CCR6 markers, and ROR-gamma-t, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of ROR-gamma-t+ and CD161+ cells were counted in the intestinal mucosa of patients with acute GVHD compared with intestinal mucosa of patients without acute GVHD, mainly found in the lamina propria but also in the epithelium of altered glands (p=0.016 and p=0.009 for ROR-gamma-t and CD161 expression respectively). Given the role of PDCs in triggering Th17-related cytokines, we sought next to determine the proportion of PDCs in intestinal biopsies from these same patients. This analysis showed a significant increase of CD123+ PDCs in the intestinal mucosa of patients with acute GVHD compared with mucosa of patients without acute GVHD (p=0.017). Moreover, we observed a significant correlation between the number of CD123+ PDCs and ROR-gamma-t or CD161 expressing cells in the intestinal mucosa of acute GVHD patients, highlighting the link between PDC and Th17 cells. Conclusion. The current study shed some light on the role of Th17 cells in the context of gastro-intestinal acute GVHD. Using well-established specific markers, we show that Th17 cells infiltrate intestinal biopsies from patients with acute GVHD. In addition, Th17 infiltration was paralleled by the infiltration of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 response in the context of gastro-intestinal acute GVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. Functional analyses are currently ongoing. Although the exact mechanism that links type I IFN production to PDC-mediated Th17 responses is still unclear in acute GVHD, these data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of acute GVHD by targeting PDCs and the Th17 response. Disclosures: No relevant conflicts of interest to declare.

Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Skin Acute Graft-Versus-Host-Disease (GVHD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4103-4103
Author(s):  
Florent Malard ◽  
Céline Bossard ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
Jacques Delaunay ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Type I ◽  
Type I Ifn ◽  
Th17 Response

Abstract Abstract 4103 Background. Acute GVHD after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. Previous studies established an important role of Th1 cells in acute GVHD pathophysiology. However, the identification of proinflammatory Th17 cells which contribute to autoimmune diseases pathophysiology, raised the issue of the role of Th17 cells in human acute GVHD. Indeed, the contribution of Th17 cells in acute GVHD was assessed in GVHD mouse models with conflicting results. In addition, the role of the PDC subset (the professional type I IFN-secreting cells), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the acute GVHD setting. This report investigated the role of Th17 cells and their interaction with PDC in cutaneous biopsies taken from patients with or without acute GVHD. Patients and Methods. Studies described in this report were performed in a single centre series of 38 patients who underwent allo-SCT for different hematological malignancies (n=37) and severe aplastic anemia (n=1). The median age of patients was 52 years (range, 17–70). The stem cell source was PBSCs in 27 cases (71%), CB in 6 cases and BM in 5 cases. 11 patients received transplant from a matched-related donor, and 27 patients from an unrelated donor. A reduced-intensity conditioning regimen was used in the majority of cases (n=29; 76%) Immunohistochemistry was performed on deparaffinized tissues sections using an indirect immunoperoxydase method. A quantitative evaluation of antigens expression was performed by counting the number of positive cells in the whole biopsy at 200 magnifications for each sample. Results. In this cohort, based on standard pathology criteria, 29 patients had a histologically proven skin acute GVHD. In all cases, biopsies were taken before initiation of systemic corticosteroid therapy. The remaining 9 patients did not have histological signs of acute GVHD (and did not develop clinical signs of acute GVHD) and thus, were used as controls. In order to identify the Th17 cell population, biopsies were tested for expression of the CD161 and CCR6 markers, and ROR-gamma-t, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of ROR-gamma-t+, CD161+ and CCR6+ cells were counted in the skin of patients with acute GVHD compared with intestinal mucosa of patients without acute GVHD, mainly found in the lamina propria but also in the epithelium of altered glands (p=0.001, p<0.0001 and p=0.01 for ROR-gamma-t, CD161 and CCR6 expression respectively).Given the role of PDCs in triggering Th17-related cytokines, we sought next to determine the proportion of PDCs in cutaneous biopsies from these same patients. This analysis showed a significant increase of BDCA2+ PDCs in the skin of patients with acute GVHD compared with skin of patients without acute GVHD (p=0.03). Moreover, we observed a strong expression of the type I IFN-inducible protein Mx1 in the skin of patients with acute GVHD compared with skin of patients without acute GVHD, reflecting the high production of type I IFN by the BDCA2+ PDCs. Conclusion. The current study shed some light on the role of Th17 cells in the context of cutaneous acute GVHD. Using well-established specific markers, we show that Th17 cells infiltrate skin biopsies from patients with acute GVHD. In addition, Th17 infiltration was paralleled by the infiltration of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 response in the context of cutaneous acute GVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. Functional analyses are currently ongoing. These data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of acute GVHD by targeting PDCs and the Th17 response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiang-Tian Meng ◽  
Yun-Yue Shi ◽  
Hong Zhang ◽  
Hong-Yan Zhou
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Allergic Conjunctivitis ◽  
Interleukin 17 ◽  
Type I ◽  
T Helper ◽  
Th2 Immune Response

Allergic conjunctivitis (AC) is a common allergic disease that is often associated with the onset of rhinitis or asthma. The incidence of AC has increased significantly in recent years possibly due to air pollution and climate warming. AC seriously affects patients’ quality of life and work efficiency. Th (T-helper) 2 immune responses and type I hypersensitivity reactions are generally considered the basis of occurrence of AC. It has been found that new subpopulations of T-helper cells, Th17 cells that produce interleukin-17 (IL-17), play an important role in the Th2-mediated pathogenesis of conjunctivitis. Studies have shown that Th17 cells are involved in a variety of immune inflammation, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. However, the role of Th17 and IL-17 in AC is unclear. This paper will focus on how T-helper 17 cells and interleukin-17 are activated in the Th2 immune response of allergic conjunctivitis and how they promote the Th2 immune response of AC.

scholarly journals Adaptive Immunity: The Role of Toll-Like Receptors

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yamaguchi R ◽  
◽  
Sakamoto A ◽  
Yamaguchi R ◽  
Haraguchi M ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Th17 Cells ◽  
Adaptive Immune Response ◽  
Toll Like Receptors ◽  
Adaptive Immune ◽  
Interleukin 23

The central mediators of the adaptive immune response are T cells. The clonal expansion of T cells required for adaptive immunity results from the innate immune response, which is triggered by the stimulation of Toll-Like Receptors (TLRs). The adaptive immune response can cause autoimmune diseases, and Th17 cells are known to contribute to several autoimmune diseases. Pathogenic Th17 cells are induced by Interleukin 23 (IL-23) and IL-1Β. Resiquimod (a TLR7/8 agonist) significantly enhances IL-23 production by human macrophages, and lipopolysaccharide (a TLR4 agonist) slightly enhances it. Interestingly, IL-23 levels are significantly attenuated after sequential stimulation with lipopolysaccharide and resiquimod, indicating cross-talk between the TLR4 and TLR7/8 signaling pathways. In this review, we discuss the pivotal role of TLRs in triggering innate immunity and inducing adaptive immunity, leading to autoimmune diseases.

THE ROLE OF PLASMA LEVELS INTERLEUKIN-6 ON MORTALITY IN NON-OBESE PATIENTS WITH NEWLY DIAGNOSED HEART FAILURE, DURING 12-MONTHS OF FOLLOW-UP

2008 ◽  
Vol 9 (1) ◽  
pp. 114-115
Author(s):  
I. Kotrogiannis ◽  
C. Chrysohoou ◽  
C. Vasiliadou ◽  
L. Papadimitriou ◽  
G. Pounis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Obese Patients ◽  
Newly Diagnosed

scholarly journals Th17 Cells in Viral Infections—Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1159
Author(s):  
Iury Amancio Paiva ◽  
Jéssica Badolato-Corrêa ◽  
Débora Familiar-Macedo ◽  
Luzia Maria de-Oliveira-Pinto
Keyword(s):  
Immune Response ◽  
Th17 Cells ◽  
Viral Infections ◽  
Critical Role ◽  
Virus Infections ◽  
Effector Functions ◽  
Epithelial Barriers ◽  
Bacteria And Fungi ◽  
Pro Inflammatory Cytokines

Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host’s immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage.

scholarly journals Epigenetics effect on pathogenesis of thyroid-associated ophthalmopathy

2021 ◽  
Vol 14 (9) ◽  
pp. 1441-1448
Author(s):  
Jia-Min Cao ◽  
◽  
Shi-Ying Hou ◽  
Xin Qi ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Autoimmune Disease ◽  
Therapeutic Strategies ◽  
Clinical Activity ◽  
Graves Disease ◽  
Clinical Activity Score ◽  
Thyroid Associated Ophthalmopathy ◽  
Non Coding Rnas

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Recent studies have found the aberrant epigenetics in TAO, including DNA methylation, non-coding RNAs, and histone modification. Many genes have an aberrant level of methylation in TAO. For example, higher levels are found in CD14, MBP, ANGLE1, LYAR and lower levels in DRD4 and BOLL. Non-coding RNAs are involved in the immune response (miR-146a, miR-155, miR-96, miR-183), fibrosis regulation (miR-146a, miR-21, miR-29), adipogenesis (miR-27) and are thought to play roles in TAO. MicroRNA is also related to the clinical activity score (miR-Let7d-5p) and may be a predictor of glucocorticoid therapy (miR-224-5p). The quantities of H4 in TAO are increased compared with euthyroid control subjects, and the role of histone modifications in Graves’ disease may lead to better understanding of its role in TAO. More studies are needed to explain the role of epigenetics in TAO and provide potential therapeutic strategies.

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