Ferroptosis as a novel alternative cell death model in Hashimoto´s thyroiditis

Area of Science:

• Endocrinology
• Immunology
• Cell Biology

Background:

• Autoimmune thyroid disorders (AITD), such as Hashimoto's thyroiditis (HT) and Graves' disease (GD), stem from immune dysregulation targeting thyroid antigens.
• Cellular damage in HT traditionally involves apoptosis, but this study explores alternative cell death pathways.

Purpose of the Study:

• To investigate ferroptosis as a novel cell death mechanism in Hashimoto's thyroiditis (HT).
• To elucidate the molecular mechanisms underlying ferroptosis in the context of HT.

Main Methods:

• Analysis of thyroid tissue from HT patients for GPx4 levels and lipid peroxidation markers.
• In vitro modeling using thyroid follicular cells (TFCs) stimulated with proinflammatory cytokines (IFN-γ, TNF-α).
• Assessment of lipid peroxidation, free iron, cell death, and protein expression related to ferroptosis and selenocysteine incorporation.

Main Results:

• HT patient thyroid tissue exhibited decreased GPx4 protein despite increased gene expression, alongside elevated lipid peroxidation products (4-HNE).
• In vitro HT models showed increased lipid peroxidation, free iron, and cell death upon cytokine stimulation, confirming ferroptosis.
• Reduced expression of PRDX6 and impaired GPx4 translation were observed, linking inflammation to ferroptosis.

Conclusions:

• Ferroptosis is a significant cell death pathway implicated in the pathogenesis of Hashimoto's thyroiditis.
• The proinflammatory environment in HT contributes to ferroptosis by disrupting GPx4 function and promoting oxidative stress.
• This finding offers new insights into HT mechanisms and potential therapeutic targets.