Cellular and molecular basis of thyroid autoimmunity

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• Autoimmune thyroid disease (AITD) is the most prevalent human autoimmune disorder, manifesting as Graves' disease or Hashimoto's thyroiditis.
• AITD involves thyroid gland lymphocytic infiltration, leading to hypothyroidism (Hashimoto's thyroiditis) or hyperthyroidism (Graves' disease) via thyrotropin receptor activation.

Purpose of the Study:

• To provide an updated overview of the molecular and cellular mechanisms driving autoimmune thyroid disease pathology.
• To explore the interplay of genetic, environmental, ncRNA, and microbiome factors in AITD pathogenesis.

Main Methods:

• Review of studies on AITD patients, animal models, and thyroid cell lines.
• Analysis of genetic variations (SNPs) in immune regulation and thyroid function genes (e.g., CD40, TSHR, FLT3, PTPN22).
• Investigation of the role of non-coding RNAs (ncRNAs) and gut microbiome in AITD.

Main Results:

• Identified key events in the loss of immune tolerance to thyroid autoantigens and signaling pathways causing thyroid destruction.
• Highlighted the contribution of specific genetic polymorphisms to AITD susceptibility.
• Underscored the clinical significance of ncRNAs and microbiome composition as diagnostic and prognostic biomarkers.

Conclusions:

• AITD pathogenesis is multifactorial, involving intricate interactions between genetic predisposition, environmental triggers, ncRNAs, and the microbiome.
• Novel biomarkers derived from ncRNAs and microbiome analysis show promise for clinical application in AITD.
• Probiotic supplementation may represent a potential therapeutic strategy for modulating thyroid function in AITD.