miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. To date, the underlying mechanisms responsible for these processes are incompletely understood. Here, we identified that miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicle (sEV) can induce Treg function defect and thyrocyte destruction though an intact response loop, favoring the progression of HT. Inactivation of miR-142-3p can effectively protect NOD.H-2h4 mice from HT development which display reduced lymphocyte infiltration, lower antibody titer, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by T lymphocyte-derived tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway through downregulating RAC1. Taken together, our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT.