The Imbalance in Th17 and Treg Cells in Polycystic Ovarian Syndrome Patients with Autoimmune Thyroiditis

Ma, Ming; Wang, Mengsi; Xu, Fang; Hao, Song-Li

doi:10.1080/08820139.2021.1915329

Cited by 13 publications

(10 citation statements)

References 25 publications

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“…They mediate apoptosis/ necrosis of thyroid follicular cells through cellular/humoral immune mechanisms (12,13,30,31). In recent years, Th17/ Treg cells have also been found to be important for thyroiditis, and several studies have shown that the imbalance of Th17/Treg cells is involved in the pathogenesis of autoimmune thyroid diseases (32)(33)(34)(35)(36). The increase in the number of Th17 cells in Hashimoto's thyroiditis correlated positively with the degree of thyroiditis (37) and damage to the thyroid structure (38).…”

Section: Discussionmentioning

confidence: 99%

“…The increase in the number of Th17 cells in Hashimoto’s thyroiditis correlated positively with the degree of thyroiditis ( 37 ) and damage to the thyroid structure ( 38 ). Th17 cells stimulate macrophages, fibroblasts, and epithelial cells to produce cytokines by secreting IL -17, which leads to apoptosis of thyroid cells ( 39 , 40 ). Blockade of IL -17 signaling significantly reduced lymphocyte infiltration in the thyroid gland of mice with experimental autoimmune thyroiditis ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

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Leptin receptor antagonist attenuates experimental autoimmune thyroiditis in mice by regulating Treg/Th17 cell differentiation

et al. 2022

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Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto’s thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto’s thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto’s thyroiditis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Leptin receptor antagonist attenuates experimental autoimmune thyroiditis in mice by regulating Treg/Th17 cell differentiation

et al. 2022

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“…The T helper profiles also contribute to the immune PCOS patients with autoimmune thyroiditis, likely causing infertility complications in these patients. 51 Treg reduction in peripheral blood of PCOS patients as a result of aberrant IL2-STAT5B-FOXP3 signaling was already established. 25 Several studies point to AIRE's role in promoting Treg induction.…”

Section: Discussionmentioning

confidence: 99%

“…Immune profile variation in PCOS is recently reported 50 and T cell dysfunction is now added to the pathogenesis of PCOS 24 . The T helper profiles also contribute to the immune etiology of PCOS‐ the bias for Th1 and Th17 and reduced Th2 and Tregs are indications of a varied inflammatory immune response in PCOS patients with autoimmune thyroiditis, likely causing infertility complications in these patients 51 . Treg reduction in peripheral blood of PCOS patients as a result of aberrant IL2‐STAT5B‐FOXP3 signaling was already established 25 .…”

Section: Discussionmentioning

confidence: 99%

Autoimmune regulator (AIRE): Takes a hypoxia‐inducing factor 1A (HIF1A) route to regulate FOXP3 expression in PCOS

Padmanabhan

Johnson

Dhyani

et al. 2022

American J Rep Immunol

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Problem Autoimmune polyendocrinopathy‐candidiasis‐ ectodermal dystrophy (APECED) pathology due to autoimmune regulator (AIRE) gene mutations leads to loss of central tolerance triggering immune attack, a factor causing infertility. One of the targets of autoimmune attack is ovary and its repercussion results in polycystic ovarian syndrome (PCOS). Although reduced Tregs have been reported in PCOS, a lacunae exists on the status of AIRE gene expression and its role in treg insufficiency via HIF1A‐FOXP3 axis in PCOS. Method of study This is a case‐control cohort study recruiting 40 normal and 40 PCOS volunteers for peripheral blood sample collection and PCOS diagnoses were based on Rotterdam Consensus criteria. AIRE and HIF1A expression status was analysed by qRT PCR and western blot. FACS analyses was conducted on AIRE silenced peripheral blood mononuclear cells (PBMCs) after Treg induction. Results Our results indicate a reduced AIRE (fold change log2 (RQ) = –2.6, P < .01) and increased HIF1A (fold change log2 (RQ) = 3.6, P < .02) in PBMCs of PCOS subjects compared to age‐matched controls. Western blot of AIRE and HIF1A corroborates with qRT PCR data. Our CHIP data demonstrate AIRE mediated HIF1A promoter regulation. Silencing of AIRE in PBMCs contributes to the upregulation of HIF1A transcripts by two‐fold (P < .0015) and downregulation in FOXP3 expression by three‐fold (P < .0017). FACS analyses revealed that silencing of AIRE reduces Tcell to Treg conversion. Conclusions Our consolidated results derive a new connection among AIRE‐HIF1A‐FOXP3 with AIRE reduction enabling increased HIF1A resulting in reduced FOXP3 in PBMCs of PCOS patients leading to Treg insufficiency.

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“…Available evidence suggests that there may be a general decline in adaptive immunity and regulatory T-cell function in PCOS (121). Recent studies have suggested that immune system dysregulation, including T-cell dysfunction (127,128), may play a role in the pathogenesis of PCOS (129).…”

Section: Adaptive Immune Response In Pcosmentioning

confidence: 99%

Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms that Disturb the Hallmarks of Health in Polycystic Ovary Syndrome

Parker¹

2023

Preprint

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Polycystic ovary syndrome (PCOS) is increasingly being characterized as an evolutionary mismatch disorder that presents with a complex mixture of metabolic and endocrine symptoms. The Evolutionary Model proposes that PCOS arises from a collection of inherited polymorphisms that have been consistently demonstrated in a variety of ethnic groups and races. In-utero developmental programming of susceptible genomic variants are thought to predispose the offspring to develop PCOS. Postnatal exposure to lifestyle and environmental risk factors results in epigenetic activation of developmentally programmed genes and disturbance of the hallmarks of health. The resulting pathophysiological changes represent the consequences of poor-quality diet, sedentary behaviour, endocrine disrupting chemicals, stress, circadian disruption, and other lifestyle factors. Emerging evidence suggests that lifestyle-induced gastrointestinal dysbiosis plays a central role in the pathogenesis of PCOS. Lifestyle and environmental exposures initiate changes that result in disturbance of the gastrointestinal microbiome (dysbiosis), immune dysregulation (chronic inflammation), altered metabolism (insulin resistance), endocrine and reproductive imbalance (hyperandrogenism), and central nervous system dysfunction (neuroendocrine, autonomic nervous system). PCOS can be a progressive metabolic condition that leads to obesity, gestational diabetes, type 2 diabetes, metabolic-associated fatty liver disease, metabolic syndrome, cardiovascular disease, and cancer. This review explores the mechanisms that underpin the evolutionary mismatch between ancient survival pathways and contemporary lifestyle factors involved in the pathogenesis and pathophysiology of PCOS.

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The Imbalance in Th17 and Treg Cells in Polycystic Ovarian Syndrome Patients with Autoimmune Thyroiditis

Cited by 13 publications

References 25 publications

Leptin receptor antagonist attenuates experimental autoimmune thyroiditis in mice by regulating Treg/Th17 cell differentiation

Leptin receptor antagonist attenuates experimental autoimmune thyroiditis in mice by regulating Treg/Th17 cell differentiation

Autoimmune regulator (AIRE): Takes a hypoxia‐inducing factor 1A (HIF1A) route to regulate FOXP3 expression in PCOS

Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms that Disturb the Hallmarks of Health in Polycystic Ovary Syndrome

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