Exosome in Hashimoto's thyroiditis: from pathogenesis to diagnostic and therapeutic potential

Hashimoto's thyroiditis (HT), the most prevalent autoimmune thyroid disorder, arises from a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation. Emerging evidence highlights exosomes-small extracellular vesicles measuring 30-150 nm-as key mediators of intercellular communication and immune modulation in autoimmune disease. In HT, exosomal HSP60 released from IFN‑γ-stimulated thyroid follicular cells acts as an autoantigen cross‑reacting with TPO and TG, promoting thyrocyte injury through antigen-antibody interactions. T‑cell-derived exosomes enriched in miR‑142‑3p impair regulatory T‑cell function and exacerbate thyrocyte destruction by suppressing RAC1 and inhibiting ERK1/2 signaling. Patient‑derived exosomes containing elevated TPO and MHC‑II activate dendritic cells via TLR2/3 and NF‑κB pathways, driving Th1/Th17 polarization while suppressing Treg differentiation. Proteomic studies further reveal distinct exosomal signatures in HT, including increased immunomodulatory proteins such as HGFL, FAK1, and PTN12. Therapeutically, inhibition of exosome release (e.g., GW4869) and the use of engineered mesenchymal stem cell-derived exosomes demonstrate promising potential for restoring immune homeostasis. Collectively, these findings position exosomes as central contributors to HT pathogenesis and highlight their value as emerging diagnostic biomarkers and targets for innovative immunotherapeutic strategies.