Extracellular vesicles from T lymphocytes induce regulatory T cell dysfunction and thyrocyte destruction in hashimoto's thyroiditis through miR-146a-5p transfer.

Authors

Yi-Nan Li, Jingxue Shen, Yinglan Feng

Published in

Molecular and cellular biochemistry. Nov 02, 2026. Epub Nov 02, 2026.

Abstract

Hashimoto's thyroiditis (HT) primarily presents with hypothyroidism due to thyrocyte destruction mediated by humoral and cellular immunity. Extracellular vesicle (EV)-encapsulated microRNAs (miRNAs or miRs) have emerged as potential biomarkers for autoimmune diseases. The aim of this study was to analyze the effect of miR-146a-5p encapsulated in T lymphocyte-derived EVs on HT and to explore the underlying mechanism. miR-146a-5p expression in T lymphocytes from patients with HT was detected, followed by correlation analysis with Th17/regulatory T cell (Treg) balance. EVs were isolated from T lymphocytes and then identified. Thyroid follicular epithelial cells, Nthy-ori 3-1, were co-cultured with EVs from T lymphocytes transfected with miR-146a-5p mimics (EVs^{miR-146a-5p mimics}) or inhibitors (EVs^{miR-146a-5p inhibitors}). The proliferation, apoptosis, and autophagy of Nthy-ori 3-1 cells in this co-culture system were subsequently determined. A mouse model of HT was developed and injected with miR-146a-5p antagomir to verify the function of miR-146a-5p in vivo. miR-146a-5p was highly expressed in T lymphocytes of patients with HT and was closely correlated with Treg dysfunction. miR-146a-5p was enriched in T lymphocyte-derived EVs and could be delivered into Nthy-ori 3-1 cells, where it curbed cell proliferation and provoked cell apoptosis. Suppression of the ERK1/2 pathway-mediated autophagy was a central mechanism that contributed to thyrocyte apoptosis. In vivo results confirmed that silencing of miR-146a-5p rescued Treg dysfunction and thyrocyte destruction, mitigating HT. Overall, miR-146a-5p shuttled by T lymphocyte-derived EVs elicits Treg dysfunction and thyrocyte destruction, which may be a key target for the treatment of HT.

PMID:
42970184
Bibliographic data and abstract were imported from PubMed on 03 Nov 2026.

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